In re Heparin Products Liability Litigation (803 F. Supp. 2d 712, 2011)

MEMORANDUM OF OPINION AND ORDER

JAMES G. CARR, Senior District Judge.

This multi-district products liability litigation arises out of the manufacture and sale by defendants of contaminated heparin. The plaintiffs allege that the use of contaminated heparin caused a myriad of adverse reactions leading to serious injuries and, in some cases, death.

Pending is defendants’ motion for summary judgment on the following categories of claims:

• Claims lacking evidence of any symptoms within sixty minutes of heparin administration;

• Claims alleging heparin-induced thrombocytopenia (HIT);

• Claims alleging sepsis or sepsis-like conditions;

• Claims alleging bleeding or clotting;

• Claims alleging injury due to administration of non-bolus doses of contaminated heparin;

• Claims alleging exposure to contaminated heparin containing less than 15% of the contaminant Oversulfated Chondroitin Sulfate (OSCS); and

• Claims falling outside the CDC case definition.

[Doc. 527].

Also pending are several Daubert challenges ancillary to the summary judgment motion. Defendants have filed a motion for exclusion of general causation testimony by plaintiffs’ experts Drs. Hoppensteadt, Jeske, Kiss, Buncher, Luke and Ohr [Doc. 528]. Plaintiffs have filed motions for exclusion of the testimony of Dr. Howard William Ory [Doc. 438] and Dr. Ronald M. Burch [Doc. 442], I also take notice of plaintiffs’ motion, which became decisional as this order was being completed, for an order to show cause relating to the licensing and board certification of Dr. Burch. [Doc. 583].

For the reasons that follow, I grant in part and deny in part the parties’ Daubert motions. I grant in part and deny in part defendants’ motion for summary judgment.

Background

A. Heparin Contamination

Heparin, one of the oldest clinical drugs still in wide-spread use, has been marketed in the United States for nearly seventy years. Over one million multi-dose vials of heparin are sold per month in the United States. Baxter Healthcare Corporation (Baxter) supplies about half the heparin sold in the United States.

An anticoagulant, heparin decreases the clotting ability of blood, thereby preventing formation of clots and stopping the growth of already existing clots. Heparin is used as a prophylaxis against blood clots among bed-ridden hospital patients, as an anticoagulant during surgeries and in catheters and pumps during procedures such as kidney dialysis, and as a treatment of such conditions as pulmonary embolism and deep-vein thrombosis.

Many patients who receive heparin have serious pre-existing medical conditions. Patients with end-stage renal disease and patients undergoing coronary artery bypass surgery make up a significant number of those receiving vial heparin.

To survive, patients with end-stage renal disease must undergo dialysis or receive a kidney transplant. There are two forms of dialysis: hemodialysis, in which a machine filters wastes, salts and fluid from the blood, and peritoneal dialysis, in which dialysate is washed in and out of the peritoneal cavity. Heparin is incorporated into both therapies.

Even when receiving dialysis, end-stage renal disease patients suffer a significant background mortality rate. Dialysis patients also commonly experience side effects such as drop in blood pressure, shortness of breath, abdominal cramps, nausea and vomiting.

A coronary artery bypass graft is an open-heart procedure that involves grafting a new artery or vein around diseased or blocked sections of the arteries in order to increase blood flow to the heart muscle tissue. A bolus dose of heparin is often administered at the outset of the procedure. Coronary artery bypass graft patients may experience side effects including drops in blood pressure and platelet counts. Complications include heart failure, heart attacks, serious arrhythmia, stroke and respiratory, renal and multiple organ failure.

Heparin is generally well-tolerated. Although laboratory monitoring is necessary to ensure its therapeutic effect and safety, it has predictable pharmacokinetics.

The most common adverse event related to heparin administration is bleeding, which is variable in severity. Serious bleeding occurs with a reported frequency of 1-3%. Heparin-induced thrombocytopenia (HIT) is another serious complication of heparin therapy. HIT is the development of thrombocytopenia (a low platelet count) associated with the administration of heparin.

When a person suffers from HIT, the immune system forms antibodies against heparin. These antibodies are bound to a protein called platelet factor 4 (PF4) and usually develop between four and fourteen days after initial exposure to heparin. HIT predisposes a patient to thrombosis, the abnormal formation of blood clots in a blood vessel. Immune-mediated HIT is a potentially life-threatening complication occurring in 1-2% of patients receiving unfractionated heparin. Hypersensitivity and allergic-type reactions are rare.

In late December, 2007, the U.S. Food and Drug Administration (FDA) and Baxter received over 350 adverse event reports associated with the use of heparin. The FDA characterized this as a marked increase from the usual number of reports associated with heparin use. This led to investigations by the U.S. Centers for Disease Control and Prevention (CDC) beginning in January, 2008.

The CDC identified a cluster of symptoms based upon initial reports of allergic-type reactions among pediatric hemodialysis patients. After the CDC solicited further reports of similar reactions among hemodialysis patients, the agency identified Baxter heparin as a common feature among the reported cases. On January 17, 2008, Baxter recalled nine multi-dose lots, and on February 29, 2008, Baxter recalled all its heparin single and multidose vials and HEP-LOCK flush products.

Intense efforts to determine the nature and source of the contaminant followed. On March 19, 2008, the FDA announced that the active pharmaceutical ingredient (API) in Baxter’s heparin had been intentionally contaminated with Oversulfated Chondroitin Sulfate (OSCS). OSCS is a synthetic compound with anticoagulant properties mimicking those of heparin. Baxter obtained this contaminated API from its Chinese supplier, defendant Scientific Protein Laboratories (SPL), and incorporated it into some of its heparin products.

B. Retrospective Studies

In December, 2008, researchers with the CDC’s Epidemic Intelligence Service and others published a retrospective study of reported adverse event data using a facility-based case-control methodology (the Blossom Study). This study resulted from the CDC’s January, 2008, investigation of the severe adverse reactions associated with heparin reported between November, 2007, and January, 2008.

Preliminary findings suggested that heparin was a possible cause of the reactions. Seeking to identify the source of the outbreak of adverse events, the CDC investigation began collecting information about adverse events and identifying control facilities (those facilities reporting no reactions).

For this investigation, the CDC defined a definite case of adverse reaction as the sudden onset of angioedema (i.e., facial swelling) or urticaria (hives) in a patient within one hour of heparin administration. It defined a probable case as the development, also within one hour of heparin administration, of hypotension, loss of consciousness, or signs and symptoms from at least two of the following categories: sensation of burning, warmth, or flushing; numbness or tingling; difficulty swallowing; shortness of breath, audible wheezing, or chest tightness; tachycardia; and nausea, vomiting, or diarrhea.

The researchers found that the adverse reactions were most often characterized by hypotension, nausea, and shortness of breath occurring within thirty minutes of administration, with a mean time to reaction of 5.1 minutes during dialysis and 15.9 minutes during cardiac treatments. The researchers observed that similar adverse reactions had been documented in the past among hemodialysis patients. Those reactions had been attributed to a variety of different causes, including dialyzer membranes, water impurities, residual disinfectants and medications. Heparin alone, however, rarely causes the symptoms observed.

The Blossom study concluded that “[h]eparin contaminated with OSCS was epidemiologically linked to adverse reactions in [the] nationwide outbreak,” and “[t]he reported clinical features of many of the cases further support the conclusion that [OSCS contaminated heparin] was the cause of the outbreak.” Use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions.

The Blossom study researchers made no determination of a causal relationship between deaths reported to the CDC and heparin administration. They noted that many deaths occurred among patients suffering from life-threatening diseases. The researchers also cautioned that the cases described likely did not encompass all cases of adverse reactions to contaminated heparin.

The Blossom study included analytic and in vitro testing of contaminated heparin vials received from surveyed facilities. These tests confirmed the findings of an earlier animal study that OSCS activates the kinin-kallikrein biological pathway in human plasma.

The kinin-kallikrein system plays a role in inflammation, blood pressure control, coagulation and pain. Activation of the kinin-kallikrein pathways in human plasma generates bradykinin, a potent vasoactive mediator that causes blood vessels to dilate, thereby lowering blood pressure. Activation of these systems can potentially result in adverse reactions.

Researchers at the FDA’s Office of Surveillance and Epidemiology published a second retrospective review in 2010 (the McMahon study). The purpose of the McMahon study was “to describe associations, patterns or signals among allergic-type heparin-associated [adverse events] that may not have been apparent in the more circumscribed sample previously investigated [ie., the Blossom study].” In considering the adverse event reports, the McMahon study abandoned the symptomatology and sixty minute restriction of the Blossom study, but it limited its focus to anaphylactoid-type reactions. The study concluded that “the mechanism of OSCS kallikrein activation fits the observed events and thus provides biological plausibility to OSCS mediated [adverse events].”

C. Procedural History

Litigation in both state and federal courts followed the contamination crisis. On June 6, 2008, the Judicial Panel on Multidistrict Litigation transferred federal heparin products liability cases to this court for consolidated pretrial proceedings.

Together with the parties, I determined that the best way to proceed was by bellwether trial process. The initial group of bellwether cases were selected based upon the case definition outlined by the CDC in the Blossom study.

The pending summary judgment motion seeks dismissal of claims of injury or death where the allegedly causative reactions are outside the CDC case definition parameters. These reactions include HIT, bleeding or clotting, sepsis, injuries with a time to onset greater than one hour after administration of contaminated heparin, and injuries involving non-bolus dosing or subcutaneous administration rather than intravenous administration. The defendants also seek summary judgment with regard to claims alleging exposure to contaminated heparin containing less than 15% OSCS.

In addition to reviewing the parties’ briefs and the numerous exhibits, I held a two-day Daubert hearing addressing the testimony of plaintiffs’ experts Dr. Debra Hoppensteadt and Dr. Joseph Kiss and defendants’ expert Dr. Ronald M. Burch. On the basis of this testimony and the record, I am now prepared to rule on the instant motions. •

Standard of Review

A party is entitled to summary judgment on motion under Federal Rule of Civil Procedure 56 where the opposing party fails to show the existence of an essential element for which that party bears the burden of proof. Celotex Corp. v. Catrett, 477 U.S. 317, 322, 106 S.Ct. 2548, 91 L.Ed.2d 265 (1986). The movant must initially show the absence of a genuine issue of material fact. Id. at 323, 106 S.Ct. 2548.

Once the movant meets that initial burden, the “burden shifts to the nonmoving party [to] set forth specific facts showing there is a genuine issue for trial.” Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 250, 106 S.Ct. 2505, 91 L.Ed.2d 202 (1986) (quoting Fed.R.Civ.P. 56(e)). Rule 56(e) “requires the nonmoving party to go beyond the [unverified] pleadings” and submit admissible evidence supporting its position. Celotex, supra, 477 U.S. at 324, 106 S.Ct. 2548.

In deciding a motion for summary judgment, I accept the opponent’s evidence as true and construe all evidence in the opponent’s favor. Eastman Kodak Co. v. Image Tech. Servs., Inc., 504 U.S. 451, 456, 112 S.Ct. 2072, 119 L.Ed.2d 265 (1992). The movant can prevail only if the materials offered in support of the motion show there is no genuine issue of a material fact. Celotex, supra, 477 U.S. at 323, 106 S.Ct. 2548. An issue is “genuine ... if the evidence is such that a reasonable party could return a verdict for the nonmoving party.” Anderson, supra, 477 U.S. at 248, 106 S.Ct. 2505.

Discussion

Baxter moves for summary judgment on seven categories of claims, arguing that plaintiffs have failed to set forth admissible evidence that contaminated heparin can cause the injuries asserted in these categories of claims.

The parties agree that plaintiffs must present evidence of both general and specific causation to prevail on their claims. “General causation is established by demonstrating, often through a review of scientific and medical literature that exposure to a substance can cause a particular diseasef,]” while specific causation “is established by demonstrating that a given exposure is the cause of an individual’s diseasef.]” Federal Judicial Center, Reference Manual on Scientific Evidence 444 (2d ed. 2000) (emphasis added); see also In re Meridia Prods. Liab. Lit., 328 F.Supp.2d 791, 798 (N.D.Ohio 2004) (citing Sterling v. Velsicol Chem. Corp., 855 F.2d 1188 (6th Cir.1988)). Thus, plaintiffs must present expert testimony to show by a preponderance of the evidence that exposure to contaminated heparin can and did cause plaintiffs’ injuries. See, e.g., Glaser v. Thompson Med. Co., 32 F.3d 969 (6th Cir.1994).

General causation is a critical threshold issue with respect to each claim. Absent credible and scientifically reliable proof of causation, plaintiffs can have no claim against defendants. E.g., Hisrich v. Volvo Cars of N. Am., Inc., 226 F.3d 445, 450, 454 (6th Cir.2000); In re Meridia Prods. Liab. Litig., 328 F.Supp.2d 791, 798 (N.D.Ohio 2004), aff'd, Meridia Prod. Liab. Litig. v. Abbott Labs., 447 F.3d 861, 868 (6th Cir.2006) (“[A] plaintiff must show that the substance to which she was exposed can cause the type of injury alleged.”).

Defendants’ motion for summary judgment alleges, inter alia, that plaintiffs cannot create a genuine issue of material fact because the testimony of their experts is inadmissible under Federal Rule of Evidence 702. I therefore must address the various Daubert challenges in order to determine whether plaintiffs have advanced credible and scientifically reliable proof of general causation. In considering the challenges to the experts and the evidence, I consider the admissibility of the evidence. I consider the sufficiency of this evidence in addressing defendants’ motion for summary judgment. See Anderson, supra, 477 U.S. at 252, 106 S.Ct. 2505.

A. Daubert Challenges

Federal Rule of Evidence 702 requires me to perform a “gate-keeping role” when considering the admissibility of expert testimony. Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 597, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993). Rule 702 provides:

If scientific, technical, or other specialized knowledge will assist the trier of fact to understand the evidence or to determine a fact in issue, a witness qualified as an expert by knowledge, skill, experience, training, or education, may testify thereto in the form of an opinion or otherwise, if (1) the testimony is based upon sufficient facts or data, (2) the testimony is the product of reliable principles and methods, and (3) the witness has applied the principles and methods reliably to the facts of the case.

Rule 702 applies not only to scientific testimony, but also to other types of expert testimony based on technical or other specialized knowledge. See Kumho Tire Co., Ltd. v. Carmichael, 526 U.S. 137, 147, 149, 119 S.Ct. 1167, 143 L.Ed.2d 238 (1999).

My gate-keeping function here is three-fold.

First, I must determine whether the witness is qualified as an expert. “When making a preliminary finding regarding an expert’s qualifications under Fed.R.Evid. 104(a), the court is to examine ‘not the qualifications of a witness in the abstract, but whether those qualifications provide a foundation for a witness to answer a specific question.’ ” Smelser v. Norfolk Southern Ry. Co., 105 F.3d 299, 303 (6th Cir.1997) (quoting Berry v. City of Detroit, 25 F.3d 1342, 1351 (6th Cir.1994)).

Second, I must determine whether the testimony is reliable. See Daubert, supra, 509 U.S. at 590, 113 S.Ct. 2786. The Court in Daubert listed several factors for consideration in assessing the reliability of scientific testimony, including:

• Whether a “theory or technique ... can be (and has been) tested”;

• Whether it “has been subjected to peer review and publication”;

• Whether, in respect to a particular technique, there is a high “known or potential rate of error” and whether there are “standards controlling the technique’s operation”; and

• Whether the theory or technique enjoys “general acceptance” within a “relevant scientific community.”

Kumho Tire, supra, 526 U.S. at 149-50, 119 S.Ct. 1167 (quoting Daubert, supra, 509 U.S. at 592-94, 113 S.Ct. 2786).

The test of reliability is, however, “flexible, and Daubert’s list of specific factors neither necessarily nor exclusively applies to all experts or in every case.” Id. at 140, 119 S.Ct. 1167. “[Whether Daubert ’s specific factors are, or are not, reasonable measures of reliability in a particular ease is a matter that the law grants the trial judge broad latitude to determine.” Id. at 153, 119 S.Ct. 1167. The focus must be on the principles and methodologies on which the expert’s opinion is based, and not on the merits of the expert’s conclusions. Daubert, supra, 509 U.S. at 594-595 n. 12, 113 S.Ct. 2786; United States v. Bonds, 12 F.3d 540, 556 (6th Cir.1993) (district courts “are not to be concerned with the reliability of the conclusions generated by valid methods, principles and reasoning.”).

Finally, I must determine whether the expert’s reasoning or methodology can properly be applied to the facts at issue: ie., whether the opinion is relevant. See Daubert, supra, 509 U.S. at 591-93, 113 S.Ct. 2786. To be relevant, the testimony must “assist the trier of fact to understand the evidence or to determine a fact in issue.” Fed.R.Evid. 702. This relevance requirement ensures that there is a “fit” between the testimony and the issue to be resolved at trial. United States v. Bonds, 12 F.3d 540, 555 (6th Cir.1993).

Rejection of expert testimony “is the exception rather than the rule.” In re Scrap Metal Antitrust Litigation, 527 F.3d 517, 531 (6th Cir.2008) (quoting Fed. R.Evid. 702 Advisory Committee’s Note, 2000 Amend.). My role as gatekeeper “is not intended to serve as a replacement for the adversary system: ‘[vigorous cross-examination, presentation of contrary evidence, and careful instruction on the burden of proof are the traditional and appropriate means of attacking shaky but admissible evidence.’ ” U.S. v. 14.38 Acres of Land, 80 F.3d 1074, 1078 (5th Cir.1996) (quoting Daubert, supra, 509 U.S. at 597, 113 S.Ct. 2786).

In assessing expert testimony, I “should also be mindful of other applicable rules.” Daubert, supra, 509 U.S. at 595, 113 S.Ct. 2786. Federal Rule of Evidence 703 provides that “[i]f the underlying data are so lacking in probative force and reliability that no reasonable expert could base an opinion on them, an opinion which rests entirely upon them must be excluded.” In re Paoli RR. Yard PCB Litig., 35 F.3d 717, 748 (quoting In re “Agent Orange” Prod. Liab. Litig., 611 F.Supp. 1223, 1245 (E.D.N.Y.1985)).

The proponent of the evidence has to establish that all of the pertinent admissibility requirements are met by a preponderance of the evidence. See Fed.R.Evid. 104(a); see also Bourjaily v. United States, 483 U.S. 171, 175-76, 107 S.Ct. 2775, 97 L.Ed.2d 144 (1987).

1. Plaintiffs’ Evidence

Defendants assert that I must exclude plaintiffs’ evidence because: 1) plaintiffs’ experts have “concede[d] that there is no scientific evidence supporting the categories of claims [outside the CDC case definition]; and 2) the evidence on which plaintiffs’ experts seek to rely is ‘insufficient as a matter of law to establish causation.’ ” [Doc. 528-1].

Defendants overstate the scope of what plaintiffs’ experts “concede.” Plaintiffs’ experts acknowledge that there are no epidemiologic studies showing an increased risk of HIT, bleeding, clotting, sepsis or death. This is not the same as conceding there is no scientific evidence whatsoever supporting the categories of claims outside the CDC case definition.

Defendants also take issue with the fact that plaintiffs’ experts often state that contaminated heparin “can” or “may” result in various adverse events, citing Ohio case law requiring an expert to express opinions on proximate cause in terms of probability. See Soldo v. Sandoz Pharm. Corp., 244 F.Supp.2d 434, 525 (W.D.Pa.2003) (collecting cases). But plaintiffs’ experts do not use the terms “can” or “may” to indicate uncertainty. Rather, this language reflects the fact that the expert opinions here address general, as opposed to specific, causation. See Meridia, 328 F.Supp.2d at 798.

Defendants argue that in vitro, animal and ecologic studies cannot be used to establish general causation, plaintiffs’ experts improperly ignore epidemiologic data, and epidemiologic evidence is necessary to prove causation in this ease,

a. Non-epidemiological Evidence

Defendants argue that the types of evidence on which plaintiffs’ expert rely, which includes in vitro studies, in vivo animal studies, ecologic studies, adverse event reports, case studies and clinical reports, are insufficient as a matter of law to establish general causation.

Other courts have held otherwise. In their view, the kinds of evidence on which plaintiffs’ rely are “all recognized and accepted scientific methodologies, used for assessing the possible side-effects and hazards associated with particular drugs and the causes of disease.” Schott v. I-Flow Corp., 696 F.Supp.2d 898, 905 (S.D.Ohio 2010) (finding general causation experts’ opinions based on published and peer reviewed cohort studies, animal studies, and in vitro studies reliable where conducting epidemiological studies would be unethical); McClellan v. I-Flow Corp., 710 F.Supp.2d 1092, 1114 (D.Or.2010) (finding that in vitro and animal studies, case series and reports are “routinely reviewed and relied upon by physicians in the normal course of their profession”); Globetti v. Sandoz Pharm. Corp., 111 F.Supp.2d 1174, 1179 (finding that, in absence of ability to conduct epidemiological studies, animal studies, published medical literature, adverse event reports, medical texts, dechallenge/re-challenge experiment data and case studies presented more than adequate evidence of a scientific nature from which a reliable conclusion could be drawn); see also, Kennedy v. Collagen Corp., 161 F.3d 1226, 1229-30 (9th Cir.1998) (finding peer reviewed articles, clinical trials and product studies, a health department investigation and differential diagnosis sufficient to support causation opinion).

Of course, “[w]hen an expert does not rely on the primary [epidemiological] methodology for establishing causation, then that places a burden on the expert to explain his choice of methodologies.” Meridia, 328 F.Supp.2d at 800 (citing Conde v. Velsicol Chem. Corp., 804 F.Supp. 972, 1025-26 (S.D.Ohio 1992)). Plaintiffs argue that it would be medically and scientifically unethical to attempt a control-group epidemiological experiment of the effects of OSCS in human beings. To do so would require administering OSCS to patients and exposing them to the possibility of injury.

Nevertheless, plaintiffs must still demonstrate that the reasoning or methodology on which their experts base their opinions is scientifically valid and properly applied to the facts in issue. Gen. Elec. Co. v. Joiner, 522 U.S. 136, 144-45, 118 S.Ct. 512, 139 L.Ed.2d 508 (1997) (holding that animal studies can be a proper foundation for an expert’s opinion but that those opinions must be sufficiently supported by the animal studies on which they purport to rely). To this end, when relying on animal, in vivo and in vitro studies, courts have required experts to “explain how such studies can be reliably extrapolated to prove comparable effects in humans.” In re Prempro Prods. Liab. Litig., 738 F.Supp.2d 887, 894 (E.D.Ark.2010) (citing Joiner, supra, 522 U.S. at 144, 118 S.Ct. 512 (1997); Allison v. McGhan Medical Corp., 184 F.3d 1300, 1313-14 (11th Cir.1999); In re Paoli R.R. Yard PCB Litig., 35 F.3d 717, 743 (3d Cir.1994)).

Courts also have expressed skepticism of causation opinions based on solely on adverse event reports, case series, case reports and case studies, but have admitted such opinions when accompanied by other reliable scientific evidence. See, e.g., Glaser v. Thompson Med. Co., 32 F.3d 969, 972 (6th Cir.1994) (holding that published studies, published articles, case reports, and the expert’s own clinical and research experience constituted sufficient reliable scientific data upon which an expert may base conclusion); In re Phenylpropanolamine Prods. Liab. Litig., 289 F.Supp.2d 1230, 1248 (W.D.Wash.2003).

Because the sum of the evidence on which an expert relies can affect the reliability of the conclusions thereby reached, I will not exclude the evidence on which plaintiffs’ experts rely before determining whether they have reached their opinions through a reliable methodology.

b. Failure to Consider Epidemiological Evidence

Defendants assert that I must exclude the testimony of plaintiffs’ experts because the epidemiological evidence contradicts the evidence on which plaintiffs’ experts rely.

Courts have rejected non-epidemiological evidence as unreliable where there is an overwhelming body of epidemiological evidence to the contrary. See, e.g., Turpin v. Merrell Dow Pharmaceuticals Inc., 736 F.Supp. 737, 743 (E.D.Ky.1990) (finding in vitro studies, in vivo animal studies, chemical studies, and human data inadmissible to demonstrate a link between Bendectin and birth defects in light of over thirty epidemiological studies concluding that no statistically significant association existed); Richardson v. Richardson-Merrell, Inc., 857 F.2d 823, 830 (D.C.Cir.1988) (“Studies of this kind, singly or in combination, are not capable of proving causation in human beings in the face of the overwhelming body of contradictory epidemiological evidence.”).

Here, however, there is no such overwhelming body of contrary epidemiological evidence. Defendants point to two epidemiological studies, neither of which were designed to determine whether there was an association between contaminated heparin and any of the conditions identified in defendants’ motion for summary judgment. Absence of proof is not proof of absence, and while these studies do not provide support for plaintiffs’ theories, neither do they contradict them. I will not, therefore, exclude plaintiffs’ evidence on these grounds.

c. Necessity of Epidemiological Evidence

I decline to categorically exclude plaintiffs’ scientific evidence solely on the basis that it is not epidemiological in nature. Daubert requires only that the expert’s methodology be sound. Meridia, 328 F.Supp.2d at 801. As the Sixth Circuit and numerous other courts have made clear, “[n]o requirement exists that a party must offer epidemiological evidence to establish causation.” In re Meridia Prods. Liab. Litig., 328 F.Supp.2d 791, 799 (N.D.Ohio 2004). Epidemiological evidence may be the “primary generally accepted methodology for demonstrating a causal relation between [a] chemical compound and a set of symptoms or a disease,” but it is not the only methodology that scientists use. Meridia, supra, 328 F.Supp.2d at 800.

Defendants insist that, while epidemiological evidence is not required to establish causation in every case, it is required in this case because all of the alleged injuries and diseases can occur in the absence of contamination.

As plaintiffs point out, the court in Meridia, supra, 328 F.Supp.2d at 799-800, rejected this rationale.

Plaintiffs in Meridia alleged that Meridia, a diet drug, caused cardiovascular injuries. Defendants moved for summary judgment on general causation arguing that the obese population using Meridia suffer from increased risk of cardiovascular conditions, and unless epidemiological studies show this risk increases with Meridia ingestion, there was no way plaintiffs could successfully attribute the condition to use of Meridia. Meridia, supra, 328 F.Supp.2d at 799.

The court in Meridia held that “epidemiological evidence is just one method of proof’ and “such evidence is not mandatory.” Id. at 800. In fact, “no court has held that epidemiological evidence is necessary to establish general causation when other methods of proof are available.” Id. at 801. This is so even where the injuries alleged may occur in the absence of the use of the drug or product. See Ashburn v. Gen. Nutrition Ctrs., Inc., 533 F.Supp.2d 770, 774 (N.D.Ohio 2008); Rider v. Sandoz Pharm. Corp., 295 F.3d 1194, 1199 (11th Cir.2002); Zuchowicz v. United States, 140 F.3d 381 (2d Cir.1999).

Again, however, as the court noted in Meridia, “[w]hen an expert does not rely on the primary methodology for establishing causation, then that places a burden on the expert to explain his choice of methodologies.” Meridia, supra, 328 F.Supp.2d 791, 800 (N.D.Ohio 2004) (internal quotations omitted). Blanket exclusion of plaintiffs’ experts is therefore inappropriate, and I shall determine whether each expert has met this burden.

2. Plaintiffs Experts

Plaintiffs offer the expert testimony of Drs. Hoppensteadt, Jeske, Kiss, Buncher, Luke and Ohr. Defendants urge the court to exclude all of these experts’ opinions, arguing that they are not qualified to offer their opinions, they rely on evidence that' is insufficient as a matter of law to establish causation, and their opinions are unreliable.

a. Dr. Debra Hoppensteadt

Dr. Hoppensteadt is a certified medical technologist and licensed clinical pathologist specializing in hematology. She holds bachelor’s and master’s degrees in medical laboratory science from the University of Illinois. She earned a doctorate of philosophy in vascular surgery from the University of London. She is a professor of pathology and pharmacology at Loyola University of Chicago Stritch School of Medicine and the technical director of the Hemostasis and Thrombosis Research Laboratories at Loyola, where she has worked since 1982. Dr. Hoppensteadt has served on editorial and review boards for numerous scientific publications and seminars and has authored or contributed to more than 490 scientific articles, books and book chapters.

The Loyola laboratory contracts with other research centers and foundations, pharmaceutical companies and federally funded programs. Its activities include the development and validation of methods of investigation into mechanisms involved in the pathogenesis of vascular and thrombotic disorders, and monitoring and studying new antithrombotic and anticoagulant drugs and their effects on the hemostatic and thrombotic processes.

As technical director, Dr. Hoppensteadt is responsible for the overall operation of the laboratories, including monitoring new drugs, consulting with physicians, interpreting test results, and developing and evaluating of drugs and medical devices.

The scientists at the Loyola laboratory, including Dr. Hoppensteadt, are part of a small group of heparin experts who began, following the identification of OSCS as the contaminant in heparin, independently to research and publish articles on the biological effects of contaminated heparin. Dr. Hoppensteadt has authored or contributed to several articles, abstracts, forums and presentations regarding contaminated heparin based on studies or research undertaken by her laboratory.

Dr. Hoppensteadt offers testimony about the chemical structure of heparin, its common uses, the manufacturing process and typical allergic responses or adverse reactions associated with unadulterated heparin. She is prepared to testify about adverse event reports received, preliminary studies to determine the nature of the contaminant, the chemical structure of OSCS, the amount of OSCS found in contaminated heparin and standard procedures that could have prevented the contamination of heparin with OSCS.

It is Dr. Hoppensteadt’s opinion that contaminated heparin triggers activation of multiple biological pathways that generate protein mediators, affecting inflammation, coagulation and immunology. This activation, she states, can result in anaphylaetoid-type responses such as those recognized by the CDC case definition. In addition, this activation, in her view, can lead to increased risk of HIT, stronger anticoagulant and bleeding effects, enhanced immunogenic effects of heparin complexes with platelet factor 4, and modification of cell signaling pathways.

She believes that activation of these overlapping biological pathways, particularly in compromised patient populations, can cause immediate or delayed reactions as well as ongoing symptomatology, which can lead to organ failure and death. She also opines that the activation of kallikrein and subsequent formation of bradykinin contributes to the pathogenesis of sepsis.

Her opinions are based on her experience and education, her own research and study of contaminated heparin, the science of immune responses and the published research of others. Her opinion draws on animal studies, in vitro studies, clinical reports, case series and adverse event reports.

i. Qualifications

As defendants acknowledge, Dr. Hoppensteadt is “an articulate and qualified pharmacologist.” [Doc. 576, at 2]. For twenty-five years she has devoted her research primarily to studying heparin. Since the contaminant in heparin was first identified as OSCS, Dr. Hoppensteadt has conducted numerous studies on the biological effects of OSCS.

I find Dr. Hoppensteadt is unquestionably qualified to testify about the pharmacological and biological effects of contaminated heparin.

Defendants argue, however, that Dr. Hoppensteadt is not qualified to offer opinions as to human causation. Citing Meridia, supra, 328 F.Supp.2d at 806, they assert that in the Sixth Circuit, a pharmacologist “is not competent for purposes of general causation.”

The district court in Meridia considered the admissibility of causation testimony of Dr. Schwartz, a pharmacologist with a doctorate in pharmacy and pharmacology. Contrary to defendants’ implied characterization of the opinion, the district court did not find that pharmacologists, as a matter of law, could not offer general causation testimony for any human injury. Rather, the district court found Dr. Schwartz lacked the necessary expertise to testify about the effects of Meridia and some of his conclusions lacked a proper foundation.

In particular, the court noted that “plaintiffs make no showing that Schwartz’s expertise in pharmacology provides him with the qualifications to comment on adverse cardiovascular events,” that Schwartz lacked expertise on obesity, and that his conclusion that Meridia caused high blood pressure relied on circular logic. Id. at 805. Dr. Schwartz’s testimony was riddled with assumptions and logical leaps: “Schwartz first starts with the conclusion that Meridia causes high blood pressure then hypothesizes about the mechanisms of how the drug caused that result. Such analysis cannot be used as evidence of causation.” Id.

The court in Meridia conducted a fact-specific inquiry in determining whether Dr. Schwartz possessed the qualifications to offer his opinions, and whether there was a proper foundation for his conclusions. The court in Meridia did not find that a pharmacologist could not offer general causation testimony, but rather that Dr. Schwartz’s testimony as an expert should be limited to the marketing and packaging of Meridia, and that his testimony would not assist the Meridia plaintiffs in creating a genuine issue of material fact with regard to causation. Id. at 806-807.

Defendants would have me infer a per se rule that a pharmacologist is not competent to testify for the purposes of general causation. But insistence on a certain kind of degree or background is “at odds with the ‘liberal thrust’ of the Federal Rules and their ‘general approach of relaxing the traditional barriers to “opinion” testimony.’ ” Daubert, supra, 509 U.S. at 588, 113 S.Ct. 2786. “The language of Rule 702 and the accompanying advisory committee notes make clear that various kinds of ‘knowledge, skill, experience, training, or education,’ qualify an expert as such.” In re Paoli R.R. Yard PCB Litig., 916 F.2d 829, 855 (3d Cir.1990).

As the court in Meridia did with Dr. Schwartz, I must assess whether Dr. Hoppensteadt’s knowledge, skill, experience, training and education support her offered opinions on the effects of contaminated heparin in humans.

Defendants are correct that the fact that Dr. Hoppensteadt regularly consults with physicians does not, of itself, give her any clinical expertise. But it is also true that, unlike Dr. Schwartz in Meridia, many of Dr. Hoppensteadt’s opinions are based on her own research, and her experience and education would enable her to connect this research to well-understood mechanisms and effects in the human body. Compare Meridia, supra, 328 F.Supp.2d at 805-806 (excluding pharmacologist testimony where expert relied solely on education, training, and experience, and showed no expertise regarding the alleged injury, adverse cardiovascular events).

Plaintiffs must still show that Dr. Hoppensteadt reliably applied her research, education and experience to the facts in reaching her opinions. Fed.R.Evid. 702 advisory committee note. But where, as here, a pharmacologist possesses the relevant expertise such that she could testify regarding well-known effects in the human body, the question shifts to whether she applied that expertise reliably.

ii. Reliability

(a) Animal and In Vitro Studies

Defendants claim that Dr. Hoppensteadt bases her analysis almost entirely on in vitro and animal studies. Such studies, according to the defendants, provide, as a matter of law, an insufficient basis for a causation opinion.

As discussed above, in vitro and animal studies may be used to show causation. See, e.g., Schott, supra, 696 F.Supp.2d at 905 (observing that animal and in vitro studies are “all recognized and accepted scientific methodologies, used for assessing the possible side-effects and hazards associated with particular drugs and the causes of disease”); McClellan, supra, 710 F.Supp.2d at 1113 (noting that case studies, in vitro and animal studies “are routinely reviewed and relied upon by physicians in the normal course of their profession, as evidenced by a review of the medical literature”).

In vitro and animal studies “can provide a reliable basis for medical and scientific opinions as long as their extrapolations are warranted.” In re Human Tissue Prods. Liab. Litig., 582 F.Supp.2d 644, 663 (D.N.J.2008); see General Elec. Co. v. Joiner, 522 U.S. 136, 144, 118 S.Ct. 512, 139 L.Ed.2d 508 (1997); In re Prempro Prods. Liab. Litig., 738 F.Supp.2d 887, 894 (E.D.Ark.2010); In re Accutane Prods. Liab., 511 F.Supp.2d 1288, 1291-92 (M.D.Fla.2007).

Dr. Hoppensteadt’s opinions are not based on either animal or in vitro studies alone. She relied on both of these types of studies in combination with eeologic studies, review of one of the epidemiological studies on which defendants rely, and reviews of the literature. “Analogy, inference and extrapolation can be sufficiently reliable when the expert’s opinion is the kind that a reasonable scientist or physician would make in a decision of importance arising in the exercise of his [or her] profession outside the context of litigation.” Monroe v. Zimmer U.S. Inc., 766 F.Supp.2d 1012, 1031 (E.D.Cal.2011) (quoting McClellan, supra, 710 F.Supp.2d at 1110). Moreover, as in Monroe and McClellan, this is a case in which it would be unethical to conduct studies on humans.

Dr. Hoppensteadt’s opinions cannot be excluded as a matter of law for her reliance on animal and in vitro studies, though plaintiffs must demonstrate the reliability of her extrapolations from these studies. See Fed. Jud. Ctr., Reference Manual on Scientific Evidence at 33 (2d ed. 2000) (“The Court is more interested in focusing on ‘how and why’ causation could be inferred from the particular evidence being proffered than in formulating per se rules about the admissibility or inadmissibility of categories of evidence to prove causation.”).

(b) Adequate Basis: Biological Mechanisms

Defendants allege that Dr. Hoppensteadt’s opinions are flawed because the in vitro studies she cites “come to conflicting conclusions about the biological effects she hypothesizes.” [Doe. 528-1, at 47], In particular, defendants state that Dr. Hoppensteadt admits that contaminated heparin does not increase plasmin or thrombinlike activity compared to heparin and that there are studies that have obtained different results with respect to whether OSCS can trigger increased thrombin. Defendants point out that heparin itself limits thrombin formation. They also state that there are conflicting studies on whether OSCS activates the complement system. Finally, they state that “studies have shown that contaminated heparin is not associated with an increase in functional antibodies.” [Doc. 528-1, at 48] (citing Cafer Adiguzel, et al., Increased Prevalence of Antiheparin Platelet Factor I Antibodies in Patients May Be Due to Contaminated Heparin, 15 Clin. App. Thromb. Hemost. 145, 148 (2009)) (emphasis in original).

In the Daubert hearings, Dr. Hoppensteadt testified that while the contaminated heparin had antithrombotic and anticoagulant effects, the OSCS also causes inflammation and activation of the contact system. Dr. Hoppensteadt explained, “when we talk about hemostasis, we have to talk about a check and balance. So depending on the patient’s predisposing factors and depending on the OSCS, the OSCS could set that balance into thrombotic balance as opposed to the antithrombotic.” [Doc. 573, at 109].

She also explained that, although the contaminant did not change the anticoagulant potency as measured by the U.S.P. type assay, this assay is “not a very specific type test.” Id. Dr. Hoppensteadt testified in deposition that studies have obtained different results with respect to whether OSCS can trigger increased thrombin, and, in her opinion, these differences resulted from differing dosages of heparin and the sensitivity of the assays performed. [Doc. 528-4, at 19].

Defendants are correct that the Adiguzel study, of which Dr. Hoppensteadt was a co-author, found no statistically significant difference in terms of the prevalence of AHPF4 antibodies as measured by the C-Serotonin Release Assay (CSRA) between normal plasma, plasma obtained from 2006-2007 (exposed to noncontaminated heparin), and plasma obtained in 2008 (exposed to contaminated heparin).

The Adiguzel study found a statistically significant difference in AHPF4 antibodies between the groups as measured by “a sandwich-type immunoassay,” GTI ELISA. The study’s authors also noted a “faster and stronger platelet aggregation in the presence of AHPF4 antibodies” in the presence of contaminated heparin as opposed to uncontaminated heparin. The study’s authors opined that the CSRA responses suggest that OSCS may be responsible for an increased generation of antibodies having a lower platelet aggregation potential, which accounted for the lack of thrombocytopenic response in the study. They concluded that the presence of OSCS in heparin may enhance immunogenic effects of heparin complexes with PF4, and stated that the clinical implications warrant further studies relative to the long-term effects of these antibodies, which also bind to heparin alone and may modulate the therapeutic actions of heparins. The Adiguzel study was subjected to peer review and publication.

Dr. Hoppensteadt’s testimony demonstrates that she has not ignored or overlooked the evidence to which defendants point. She explains her rationale for nevertheless reaching the conclusions she reaches about the biological mechanisms at work in these studies. The Supreme Court in Daubert “intended to exclude ‘junk science’ — unsupported testimony or evidence cloaked in the credentials of a testifying expert — that would confuse or mislead rather than ‘assist the trier of fact.’ ” McClellan, supra, 710 F.Supp.2d at 1101 (quoting Best v. Lowe’s Home Ctrs., Inc., 563 F.3d 171, 176-77 (6th Cir.2009)). The fact that different studies have obtained different results does not render Dr. Hoppensteadt’s opinions “junk science.”

“There are no certainties in science,” Daubert, 509 U.S. at 590, 113 S.Ct. 2786, and establishing reliability does not mean that plaintiffs must prove that the assessments of their experts are correct. McClellan, supra, 710 F.Supp.2d at 1101— 102, 1106. Perceived weaknesses in the conclusions, such as those identified here by defendants, go to weight rather than to admissibility. See McClellan, supra, 710 F.Supp.2d at 1106 (“Importantly, it is not the court’s role to decide whether the proffered testimony sufficiently proves [causation]; rather, it is the court’s duty to ensure that the proffered testimony is sufficiently reliable to be admitted at trial for consideration by the trier of fact.”),

(c) Adequate Basis: Effects in Humans

Defendants assert that Dr. Hoppensteadt’s opinions are completely unsupported as to the resulting human effects of these biological mechanisms. Defendants argue that Dr. Hoppensteadt has no scientific basis for her opinions that either: 1) increased kallikrein activity or feedback loops occur in humans; or 2) such increased kallikrein activity in turn causes adverse clinical effects.

(i) Occurrence in Humans

Defendants recite that there are no studies either looking at the effects of OSCS in causing feedback loops or measuring any compliment system activation in human beings administered OSCS. They also point to Dr. Hoppensteadt’s acknowledgment that “there’s substances in human beings that prevent kallikrein from leading to clinical symptoms.” Based on these facts, defendants assert that it is “well-settled science ... that the mechanism upon which plaintiffs rely is not plausible in humans or animals.” [Doc. 576, at 5] (emphasis in original).

Dr. Hoppensteadt explained that she relied on published studies and her own research in forming her opinion that increased kallikrein activity and feedback loops occur in human beings. The Kishimoto study showed that OSCS caused contact and complement activation. Specifically, the Kishimoto study found that OSCS directly activated the kinin-kallikrein pathway in human plasma, leading to the generation of bradykinin, and that OSCS also generated the anaphylatoxins C3a and C5a. In the study, OSCS contaminated heparin and synthetically-derived OSCS both induced hypotension when administered by infusion in swine.

Plaintiffs contend several studies support Dr. Hoppensteadt’s conclusion about the occurrence of the biological mechanism in humans. Some of the studies accepting that these mechanisms are at work in human beings exposed to OSCS contaminated heparin are the same defendants on which seek to rely to block plaintiffs’ claims. The Blossom study “found similar biologic activity among multiple vials of heparin that were known to result in adverse reactions, and the clinical picture described among the outbreak cases nationally is consistent with the biologic mediators previously identified in response to OSCS.”

The McMahon study, another epidemiologic study of contaminated heparin, also concluded that “the mechanism of OSCS kallikrein activation fits the observed events and thus provides biological plausibility to OSCS mediated AEs.”

In addition to these studies, Dr. Hoppensteadt’s opinions rest on her research, involving both in vitro and animal studies. Dr. Hoppensteadt and other researchers have relied for the most part on animal and in vitro tests in researching the effects of OSCS contaminated heparin for two reasons. First, as already noted, it would be unethical to test OSCS in human beings. Second, identifying the appropriate patient groups to conduct epidemiological studies would be both difficult and expensive. Nonetheless, plaintiffs retain the burden of demonstrating that Dr. Hoppensteadt has appropriately extrapolated from these studies.

Dr. Hoppensteadt explained that “pigs are similar to similar to humans ... [T]his pig model ... is an established model that’s used for cardiopulmonary bypass surgery because it’s a large animal and because the amount of blood that is needed to be drawn to do these analysis.” [Doc. 573, at 152]. Use of pigs is further supported by the Kishimoto study. As part of this study, researchers screened plasma samples from various species. These samples indicated that swine and humans are sensitive to the effects of OSCS in a similar manner.

As the Federal Judicial Center’s Reference Manual on Scientific Evidence, at 410, notes, “[i]n qualitative extrapolation, one can usually rely on the fact that a compound causing an effect in one mammalian species will cause it in another species.”

Dr. Hoppensteadt testified that the in vitro studies would see a different degree of activation than would be present in the human body. [Doc. 573, at 156]. It is her opinion that, depending on the individual patient, the degree of activation in the human body would be greater than that seen in the test-tube due to the presence of white blood cells, red blood cells and endothelial cells. Id. She explained that her extrapolations from the in vitro studies are “based on what we know about the well-established feedback loop systems.” [Doc. 573, at 150].

Dr. Hoppensteadt has followed reliable methodology in reaching her opinions that contaminated heparin can cause contact and complement activation in human beings.

(ii) Adverse Effects in Humans

Defendants argue that even if Dr. Hoppensteadt can opine that contaminated heparin activates such pathways in humans, she cannot give a reliable scientific opinion as to any adverse effects caused by such activation. Defendants therefore seek exclusion of Dr. Hoppensteadt’s testimony as to general causation of bleeding, clotting, HIT, sepsis and symptoms occurring after sixty minutes, arguing that such testimony is speculative. Defendants also seek exclusion of Dr. Hoppensteadt’s testimony regarding dosing, specifically that any concentration of contamination in heparin can cause harm and that subcutaneous administration can result in harm.

As discussed above, plaintiffs must demonstrate that Dr. Hoppensteadt based her opinions about adverse effects in human beings on reliable science. First, as a pharmacological researcher rather than a physician, she must be able to explain how she reached her opinions on effect. Second, where her opinions on adverse effects in humans derives from animal and in vitro studies, she must explain why extrapolation to human beings is appropriate,

(aa) Bleeding

Dr. Hoppensteadt’s proffered opinions on the bleeding effects of contaminated heparin are based on reliable methodology. She derives her opinion, in part, on a publication based on in vitro and in vivo (rat) studies performed in her laboratory. The in vitro studies showed that OSCS exhibited measurable anti-coagulant activity and produced supra-additive effects in the presence of heparin. In the animal models of thrombosis and bleeding, the contaminated heparin produced stronger anti-coagulant effects than heparin.

Dr. Hoppensteadt testified that the biological mechanisms predicted such a response, explaining that “[i]f you have activation of coagulation system in the feedbacks that are occurring and you have a decrease in the fibrinolytic inhibitors, based on the specific disease of the patient, you can end up with a propensity of the patient to bleed.” [Doc. 573, at 66]. In doing so, she identifies the particular patient-specific factor, decrease in fibrinolytic inhibitors, that would interact with the biological mechanism identified to cause the result in the patient.

Other studies also acknowledge the existence and probable mechanism of bleeding effects associated with contaminated heparin. Dr. Hoppensteadt indicated that there is no dispute in the scientific community that OSCS contaminated heparin can cause an increased risk of bleeding complications. [Doc. 573, at 66].

Dr. Hoppensteadt acknowledged that bleeding is a known risk of heparin, even apart from contamination. She also acknowledged that she had not reviewed any specific cases of patient bleeding. Her opinion is nevertheless sufficiently reliable to be admissible under Rule 702. See In re Paoli, supra, 35 F.3d at 744 (“[Plaintiffs] do not have to demonstrate to the judge by a preponderance of the evidence that the assessments of their experts are correct, they only have to demonstrate by a preponderance of the evidence that their opinions are reliable.”).

(bb) Clotting

Defendants seek to exclude testimony by Dr. Hoppensteadt regarding clotting effects caused by contaminated heparin. The defendants appear to refer to clotting effects distinguishable from HIT— that is, clotting resulting from any reduced efficacy of contaminated heparin as opposed to clotting induced by contaminated heparin. Dr. Hojppensteadt’s expert report does not discuss this effect, and plaintiffs do not make any showing that any such opinion offered by Dr. Hoppensteadt is based on reliable methodology. Dr. Hoppensteadt may not testify as to such clotting effects.

(cc) HIT

It is Dr. Hoppensteadt’s opinion that OSCS contaminated heparin causes an increased risk of HIT. Dr. Hoppensteadt explained that this opinion is based on the Adiguzel study conducted at Loyola, which she co-authored, and a review of relevant scientific literature on contaminated heparin and HIT.

The Adiguzel study looked at blood samples of patients undergoing hemodialysis. The study found that the group treated during the contamination period experienced a substantial increase in the incidence of the heparin platelet factor 4 antibody. Dr. Hoppensteadt testified that none of the patients in the study actually experienced the drop in platelet count signifying the development of HIT. She and her co-authors believe, however, that the increase in these antibodies may increase the risk of these patients to develop HIT.

Dr. Hoppensteadt supports this opinion with two articles by Drs. Greinacher and Warkentin. Drs. Greinacher and Warkentin are well-respected in the field of HIT. Dr. Hoppensteadt testified that their textbook, Heparin-Induced Thrombocytopenia, “is considered the Bible when it comes to heparin induced thrombocytopenia.” [Doc. 573, at 70].

In a letter to the editor responding to the Kishimoto study, Drs. Greinacher and Warkentin discussed the likelihood that OSCS, a hyper-sulfated polysaccharide, could induce HIT. They stated that during the period of contamination, they observed a substantial increase in laboratory-confirmed heparin-induced thrombocytopenia in Germany, but not in Canada. They suggested that this association may reflect differences in distribution of OSCS-contaminated heparin, as Canada saw only a minimal recall of products and no reports of anaphylactic reactions.

Drs. Greinacher and Warkentin followed this letter to the editor with an article arguing that OSCS-contaminated heparin could increase the risk of HIT. They wrote that the discovery of OSCS in heparin “recalled an intriguing finding in the early history of HIT in which a hypersulfated chondroitin sulfate (essentially identical to OSCS) formerly used to treat degenerative arthritis, was also identified to cause a disorder identical to HIT.” They explained that “[t]he very high DS [degree of sulfation] of OSCS (4.0) contaminating UFH [unfractionated heparin] is a key feature supporting a higher immunization rate compared with non-contaminated UFH.”

Dr. Hoppensteadt explained that the article was referring to a case study on Arteparon, which reported that a patient receiving the hypersulfated chondroitin sulfate was more prone to thrombosis because of the positive charge of the platelet factor 4 and the negative charge .of the hypersulfated chondroitin sulfate. [Doc. 573, at 72].

Dr. Hoppensteadt also discussed more recent studies examining OSCS’s ability to induce thrombin generation, and noted that a paper authored by Qian, et aZ. also concluded that the effects seen in their studies suggest a higher incidence of HIT among patients receiving contaminated heparin. [Doc. 573, at 72], Dr. Hoppensteadt also testified that there is no dispute in the scientific literature that OSCS can cause an increased risk of HIT. Id.

Dr. Hoppensteadt’s opinion that OSCS contaminated heparin increases the risk of HIT is supported by her research and the published studies of others. Looking at any one of these studies, alone and without cognizance of the others, a judge would be unable to identify a reliable basis for concluding that contaminated heparin increases the risk of HIT. But looking at them together, the picture is very different.

Courts have admitted expert testimony as reliable where experts extrapolate their opinions from their knowledge and experience combined with a review of the relevant scientific literature. See, e.g., McClellan, supra, 710 F.Supp.2d at 1131. Dr. Hoppensteadt has done so here, and I find that her opinions as to HIT are sufficiently reliable. This evidence may not provide as conclusive a foundation as an epidemiological study, but that fact goes to weight, rather than admissibility.

(dd) Sepsis

Dr. Hoppensteadt opines that contaminated heparin can cause a sepsis-like response or aggravate sepsis or disseminated intravascular coagulation (DIC). There has been no study that has looked at OSCS contaminated heparin and its effects in septic patients.

Dr. Hoppensteadt bases her opinion on literature regarding “feedback loops” and the fact that OSCS contaminated heparin activates the complement system. Dr. Hoppensteadt explained that “complement activates inflammation. Inflammation then is able to, through the feedback loops, activate coagulation. And then we get this almost like a snowball effect.” [Doc. 573, at 64], She explained that because of all the activation, the symptoms can present like a patient who has an infection — “the patient’s response in the coagulation in the blood is very similar to what we see in patients with an infection.” [Doc. 573, 64].

Dr. Hoppensteadt presents nothing that would link the feedback loop responses she theorizes based on the literature to patients exposed to contaminated heparin. She has done no experiments demonstrating the ability of OSCS or OS