Overlay

Hereditary and Acquired Hypercoagulability

Hereditary and Acquired Hypercoagulability

No Results

No Results

processing….

Patients with acquired hypercoagulable states or hereditary thrombophilia are more likely to develop clots, venous thrombosis, and arterial thrombosis, than healthy individuals. Venous thrombosis and pulmonary embolism are associated with significant morbidity and mortality.

The most common acquired risk factors for hypercoagulability and thrombosis are as follows [1] :

Given the high prevalence of obesity and diabetes in the United States, and the aging of the population, the incidence of thrombosis is likely to increase.

Idiopathic (unprovoked) venous thrombotic events are defined as the occurrence of venous thrombosis in the absence of any of the risk factors listed above. About 50% of patients presenting with a first idiopathic venous thrombosis have an underlying thrombophilia.

Hereditary thrombophilias should be suspected in individuals with a history of recurrent thromboembolism, thrombosis at a young age, and/or a family history of thrombosis. Hereditary thrombophilias include the following:

Deficiencies of anticoagulant factors may also be acquired.

The objectives of this article are to provide an overview of hereditary thrombophilia and acquired hypercoagulability, to discuss indications for initiating a workup, and to review the selection and interpretation of laboratory tests for these disorders. The indications and options for anticoagulant therapy and prophylaxis, as well as the advantages and adverse effects of low molecular weight heparin (LMWH), direct thrombin, and factor Xa inhibitors are discussed.

For patient education information, see Blood ClotsInherited Blood-Clotting Problems, and the Deep Vein Thrombosis Health Center.

Hemostasis is highly regulated to maintain a delicate balance between controlling bleeding in response to injury and avoiding excess procoagulant activity, to prevent hypercoagulability and thrombosis. The Virchow triad identifies the three underlying factors that are thought to contribute to thrombosis: hypercoagulability, hemodynamic dysfunction (ie, stasis—from immobilization or peripheral venous obstruction—or turbulence), and endothelial injury/dysfunction.

Hypercoagulability can result from the release of procoagulants from tumor cells or the presence of antiphospholipid antibodies (lupus anticoagulants). Insufficient inactivation of procoagulants due to impaired regulatory antithrombotic pathways can result in hypercoagulability. The presence of factor V Leiden or a mutant prothrombin can cause hypercoagulability.  

The neutralization of activated factor Xa and thrombin are impaired in antithrombin (AT) deficiency. The formation of activated protein C (APC), which is a key down-regulator of factor V and factor VIII, may be impaired by protein C deficiency or protein S deficiency. Such deficiencies may be hereditary or acquired. [2] The ability of APC to inactivate factor V and factor VII can be impaired in individuals with mutant factor V such as factor V Leiden. This is known as APC resistance. Individuals with a mutant prothrombin (variously termed prothrombin G20210A, prothrombin G2010A, and mutant factor II) generate excess prothrombin that is associated with hypercoagulability.

Normal endothelium provides a non-thrombotic surface. Injury to endothelium is accompanied by loss of protective molecules and expression of adhesive molecules, procoagulant activity, and mitogenic factors, leading to development of thrombosis, smooth muscle cell migration, and proliferation and atherosclerosis. [3] In Behcet disease, a generalized autoimmune vasculitis and endothelial dysfunction occurs, with protean consequences that include  thrombosis, mucocutaneous lesions, uveitis, and neurological abnormalities.

Thrombosis during pregnancy can be due to increased procoagulant factors, impaired fibrinolysis, venous stasis, and endothelial cell injury. [4] The risk of thrombosis is increased in patients on hormone replacement therapy. However, whether this risk is due to increased procoagulants or the presence of an underlying thrombophilia is not clear. [5]

Lupus anticoagulants are antiphospholipid antibodies that are associated with acquired hypercoagulability. The mechanisms for hypercoagulability in these patients remains poorly understood, but alteration of the regulation of hemostasis and endothelial cell injury might be responsible. [6, 7, 8] The inappropriate name for these antibodies is due to their initial discovery in patients with lupus—although they can also occur in individuals without lupus—and to their anticoagulant effect in vitro.

Non-O blood type is associated with an approximately two-fold increase in risk for venous thrombembolism. An inherited thrombophilic condition in association with non-O blood type further increases risk. A weaker, less well documented, association exists between non-O blood type and arterial thrombosis. [9]

In addition to thrombophilias resulting from individual mutations, an inherited susceptibility to venous thromboembolism may result from multigenic action. Research on multiple polymorphisms within the anticoagulant, procoagulant, fibrinolytic, and innate immunity pathways confirms a complex interrelationship that appears to increase the risk of venous thromboembolism. [10]

Activated protein C (APC) resistance

The ability of APC to inactivate factor V and factor VIII can be impaired in individuals with mutant factor V, such as factor V Leiden.  This is known as APC resistance. Individuals with a mutant prothrombin (variously termed prothrombin 20210A, prothrombin G2010A, and mutant factor II) generate excess prothrombin that is associated with hypercoagulability. [11]

Factor V Leiden

Factor V Leiden is resistant to APC and hence not inactivated (APC resistant). About 20-60% of patients with thromboembolism have a form of APC resistance, and factor V Leiden is responsible for 95% of APC resistance. 

Factor V Leiden (named after the city in the Netherlands where it was first identified, in 1994) results from a specific point mutation in the factor V gene, which is located in the long arm of chromosome one. Glutamine (Q) is substituted for arginine (R)-506 in the heavy chain of factor V (R506Q).  The amino acid substitution alters the APC cleavage site on factor V, causing a partial resistance to inactivation. 

About 5% of Caucasian Americans are heterozygous carriers of factor V Leiden. The carrier frequency among African Americans, Asian Americans, and Native Americans is less than 1% and in Hispanics is 2.5%. Carrier frequency is especially high—up to 14%—in whites of Northern European and Scandinavian ancestry. Inheritance is autosomal dominant. Most heterozygote carriers are asymptomatic while homozygotes have a high incidence of clinical thrombosis. [12]

The 5% of APC resistance not due to factor V Leiden results from a variety of factors. These include other genetic mutations, as well as acquired conditions such as pregnancy, oral contraceptives, and lupus anticoagulant, all of which may also cause APC resistance. [12]

Prothrombin G20210A

Prothrombin G20210A is a polymorphism in a noncoding region (nucleotide 20210A) of the factor II (prothrombin) gene that consists of replacement of guanine with adenine, and results in elevated prothrombin levels. This mutation occurs primarily in Caucasians. Heterozygotes are at minimal risk for thrombosis, but homozygotes are 2- to 3-fold increased risk for developing thrombosis.

Additional risks

While persons who are heterozygous for factor V Leiden and prothrombin G20210A are at minimal risk for thrombosis, the presence of a second risk factor such as immobilization and pregnancy greatly increases the risk for thrombosis. The screening of patients for mutant Factor V and prothrombin during pregnancy and prior to initiation of hormone replacement therapy to determine whether prophylactic anticoagulation is indicated appears to be logical, but it is controversial.

United States

Lupus anticoagulants and antiphospholipid syndromes are present in 4-14% of the population. Table 1 shows the incidence of hereditary hypercoagulable disorders in the general population and the risk for thrombosis and recurrent thrombosis. [13, 14] Other underlying risk factors are elevated levels of factor VIII, fibrinogen, and other coagulation factors. Increases in type-1 plasminogen activator inhibitor (PAI-1), D-dimers, and homocysteine are also reported to be risk factors.

Table 1.  Prevalence of Acquired or Hereditary Hypercoagulable Disorders and Risks of Venous Thrombosis. (Open Table in a new window)

Condition

Prevalence in General Population (%)

Relative Risk of VTE (%)

Relative Risk of Recurrent VTE (%)

Factor V Leiden

(heterozygous)

3-7

4.3

1.3

Prothrombin 20210A

(heterozygous)

1-3

1.9

1.4

Protein C deficiency

(heterozygous)

0.02-0.05

11.3

2.5

Protein S deficiency

(heterozygous)

0.01-1

32.4

2.5

Antithrombin deficiency

(heterozygous)

0.02-0.04

17.5

2.5

VTE = Venous thromboembolism

A study by Couturaud et al sought to identify risk factors and quantify the risk of venous thromboembolism in first-degree relatives of patients with a first episode of unprovoked venous thromboembolism. [14] The investigators found a prevalence of 5.3% of previous venous thromboembolism in the first-degree relatives. The strongest predictor of venous thromboembolism in this group was thrombosis at a young age. However, the presence of factor V Leiden or G20210A prothrombin genes in patients were weak independent predictors of venous thromboembolism in relatives. [14]

Morbidity and mortality in patients with hypercoagulable states and thrombophilia are primarily due to venous thrombosis and pulmonary embolism. Pulmonary embolism is associated with a 1-3% mortality rate. The incidence of factor V Leiden and prothrombin 20210A is significantly greater than that of protein C, protein S, and antithrombin III (ATIII) deficiencies. However, the risk of venous thrombosis in protein C, protein S, and antithrombin III (ATIII) deficiencies is greater than in factor V Leiden and prothrombin 20210A, as shown in Table 1, above.

The risk for thrombosis can be markedly increased in patients with two or more risk factors for thrombosis. Any multiplicity of risk factors, whether hereditary thrombophilias or acquired risks, increases the risk for thrombosis.

For details on the effects of race and sex on hereditary and acquired hypercoagulability, see the following articles [15, 16] :

The risk for thrombosis increases with age and associated immobility.

Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet. 1999 Apr 3. 353(9159):1167-73. [Medline].

Hillarp A, Dahlback B, Zoller B. Activated protein C resistance: from phenotype to genotype and clinical practice. Blood Rev. 1995 Dec. 9(4):201-12. [Medline].

Wu KK, Thiagarajan P. Role of endothelium in thrombosis and hemostasis. Annu Rev Med. 1996. 47:315-31. [Medline].

Colman-Brochu S. Deep vein thrombosis in pregnancy. MCN Am J Matern Child Nurs. 2004 May-Jun. 29(3):186-92. [Medline].

[Guideline] Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb. 141 (2 Suppl):e691S-e736S. [Medline]. [Full Text].

Rand JH, Wolgast LR. Antiphospholipid Syndrome. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop H, Weitz J, Anastasi J, eds. Hemostasis and Thrombosis. 6th ed. Philadelphia, PA: Elsevier/Saunders; 2013. 2025-38.

Ortel TL. Thrombosis and the antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program. 2005. 462-8. [Medline]. [Full Text].

Triplett DA. Antiphospholipid antibodies. Clin Adv Hematol Oncol. 2003 Dec. 1(12):726-30. [Medline].

Franchini M, Mannucci PM. ABO blood group and thrombotic vascular disease. Thromb Haemost. 2014 Dec. 112 (6):1103-9. [Medline].

Heit JA, Cunningham JM, Petterson TM, et al. Genetic variation within the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways as risk factors for venous thromboembolism. J Thromb Haemost. 2011 Jun. 9(6):1133-42. [Medline]. [Full Text].

Eroglu A, Egin Y, Cam R, Akar N. The 19-bp deletion of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden, prothrombin G20210A polymorphisms in cancer patients with and without thrombosis. Ann Hematol. 2009 Jan. 88(1):73-6. [Medline].

Mayo Clinic. Activated Protein C Resistance V (APCRV). Mayo Medical Laboratories. Available at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/81967. Accessed: January 5, 2018.

Heit JA. Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007. 127-35. [Medline]. [Full Text].

Couturaud F, Leroyer C, Julian JA, et al. Factors that predict risk of thrombosis in relatives of patients with unprovoked venous thromboembolism. Chest. 2009 Jul 10. epub ahead of print. [Medline].

Lijfering WM, Veeger NJ, Middeldorp S, et al. A lower risk of recurrent venous thrombosis in women compared with men is explained by sex-specific risk factors at time of first venous thrombosis in thrombophilic families. Blood. 2009 Sep 3. 114(10):2031-6. [Medline]. [Full Text].

Roberts LN, Patel RK, Arya R. Venous thromboembolism and ethnicity. Br J Haematol. 2009 Aug. 146(4):369-83. [Medline].

Hong SN, Yun HC, Yoo JH, Lee SH. Association Between Hypercoagulability and Severe Obstructive Sleep Apnea. JAMA Otolaryngol Head Neck Surg. 2017 Oct 1. 143 (10):996-1002. [Medline].

Cushman M. Inherited risk factors for venous thrombosis. Hematology Am Soc Hematol Educ Program. 2005. 452-7. [Medline]. [Full Text].

Aiach M, Emmerrich J. Thrombophilia genetics. Colman RW, Marder VJ, Clowes AW, et al, eds. Hemostasis and Thrombosis. 5th ed. Philadelphia, Pa: Lippincott, Williams and Wilkins; 2006. 779-93.

Colucci G, Tsakiris DA. Thrombophilia Screening. Clin Appl Thromb Hemost. 2017 Jan 1. 1076029616683803. [Medline].

Pruthi RK. Optimal utilization of thrombophilia testing. Int J Lab Hematol. 2017 May. 39 Suppl 1:104-110. [Medline].

van Ommen CH, Nowak-Göttl U. Inherited Thrombophilia in Pediatric Venous Thromboembolic Disease: Why and Who to Test. Front Pediatr. 2017. 5:50. [Medline]. [Full Text].

Straczek C, Oger E, Yon de Jonage-Canonico MB, et al. Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration. Circulation. 2005 Nov 29. 112(22):3495-500. [Medline]. [Full Text].

Urbanus RT, de Groot PG. Antiphospholipid antibodies–we are not quite there yet. Blood Rev. 2011 Mar. 25(2):97-106. [Medline].

Bates SM. Management of pregnant women with thrombophilia or a history of venous thromboembolism. Hematology Am Soc Hematol Educ Program. 2007. 143-50. [Medline]. [Full Text].

Connors JM. Thrombophilia Testing and Venous Thrombosis. N Engl J Med. 2017 Dec 7. 377 (23):2298. [Medline]. [Full Text].

Douketis J, Tosetto A, Marcucci M, et al. Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis. BMJ. 2011 Feb 24. 342:d813. [Medline]. [Full Text].

Kearon C, Julian JA, Kovacs MJ, et al. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial. Blood. 2008 Dec 1. 112(12):4432-6. [Medline]. [Full Text].

Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep. 126(3 suppl):188S-203S. [Medline]. [Full Text].

Rühle F, Stoll M. Advances in predicting venous thromboembolism risk in children. Br J Haematol. 2017 Dec 19. 82 (1):25-6. [Medline].

Warkentin TE. Agents for the treatment of heparin-induced thrombocytopenia. Hematol Oncol Clin North Am. 2010 Aug. 24(4):755-75, ix. [Medline].

Adam SS, McDuffie JR, Lachiewicz PF, Ortel TL, Williams JW. Comparative Effectiveness of Newer Oral Anticoagulants and Standard Anticoagulant Regimens for Thromboprophylaxis in Patients Undergoing Total Hip or Knee Replacement [Internet]. VA Evidence-based Synthesis Program Reports. 2012 Dec. [Medline].

Perez A, Merli GJ. Novel Anticoagulant Use for Venous Thromboembolism: A 2013 Update. Curr Treat Options Cardiovasc Med. 2013 Feb 6. [Medline].

Dobesh PP, Oestreich JH. Novel Direct-Acting Anticoagulants for Risk Reduction in ACS. J Pharm Pract. 2012 Nov 19. [Medline].

Merli GJ. The new oral anticoagulants: a challenge for hospital formularies. Hosp Pract (Minneap). 2012 Aug. 40(3):126-8. [Medline].

Komócsi A, Vorobcsuk A, Kehl D, Aradi D. Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2012 Nov 12. 172(20):1537-45. [Medline].

Kar S, Bhatt DL. Anticoagulants for the treatment of acute coronary syndrome in the era of new oral agents. Coron Artery Dis. 2012 Sep. 23(6):380-90. [Medline].

Rajasekhar A, Beyth R, Crowther MA. Newer anticoagulants in critically ill patients. Crit Care Clin. 2012 Jul. 28(3):427-51, vii. [Medline].

Lee AY. Treatment of established thrombotic events in patients with cancer. Thromb Res. 2012 Apr. 129 Suppl 1:S146-53. [Medline].

Cohen AT, Gurwith MM, Dobromirski M. Thromboprophylaxis in non-surgical cancer patients. Thromb Res. 2012 Apr. 129 Suppl 1:S137-45. [Medline].

Vande Griend JP, Marcum ZA, Linnebur SA. A year in review: new drugs for older adults in 2011. Am J Geriatr Pharmacother. 2012 Aug. 10(4):258-63. [Medline].

Burke DA, Warraich HJ, Pinto DS. Which antithrombin for whom? Identifying the patient population that benefits most from novel antithrombin agents. Curr Cardiol Rep. 2012 Aug. 14(4):493-501. [Medline].

Di Nisio M, Middeldorp S, Büller HR. Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8. 353 (10):1028-40. [Medline].

Baglin T, Barrowcliffe TW, Cohen A, Greaves M. Guidelines on the use and monitoring of heparin. Br J Haematol. 2006 Apr. 133(1):19-34. [Medline]. [Full Text].

Harenberg J. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? Yes. J Thromb Haemost. 2004 Apr. 2(4):547-50. [Medline]. [Full Text].

Bounameaux H, de Moerloose P. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? No. J Thromb Haemost. 2004 Apr. 2(4):551-4. [Medline]. [Full Text].

[Guideline] Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb. 141 (2 Suppl):e419S-94S. [Medline]. [Full Text].

[Guideline] Kitchen S, Gray E, Mackie I, Baglin T, Makris M, BCSH committee. Measurement of non-coumarin anticoagulants and their effects on tests of Haemostasis: Guidance from the British Committee for Standards in Haematology. Br J Haematol. 2014 Sep. 166 (6):830-41. [Medline]. [Full Text].

Cho L, Kottke-Marchant K, Lincoff AM, et al. Correlation of point-of-care ecarin clotting time versus activated clotting time with bivalirudin concentrations. Am J Cardiol. 2003 May 1. 91(9):1110-3. [Medline].

Welsby IJ, McDonnell E, El-Moalem H, Stafford-Smith M, Toffaletti JG. Activated clotting time systems vary in precision and bias and are not interchangeable when following heparin management protocols during cardiopulmonary bypass. J Clin Monit Comput. 2002 Jul. 17(5):287-92. [Medline].

Chang LC, Lee HF, Yang Z, Yang VC. Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (I): preparation and characterization. AAPS PharmSci. 2001. 3(3):E17. [Medline].

Schick BP, Maslow D, Moshinski A, San Antonio JD. Novel concatameric heparin-binding peptides reverse heparin and low-molecular-weight heparin anticoagulant activities in patient plasma in vitro and in rats in vivo. Blood. 2004 Feb 15. 103(4):1356-63. [Medline]. [Full Text].

Welsby IJ, Stafford-Smith M. Monitoring direct thrombin inhibitors: time for standardization. Anesthesiology. 2004 Oct. 101(4):1048-9. [Medline].

Weitz JI. New anticoagulants for treatment of venous thromboembolism. Circulation. 2004 Aug 31. 110(9 suppl 1):I19-26. [Medline]. [Full Text].

Connors JM. Antidote for Factor Xa Anticoagulants. N Engl J Med. 2015 Dec 17. 373 (25):2471-2. [Medline]. [Full Text].

Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6. 375(9717):807-15. [Medline].

Romualdi E, Ageno W. Oral Xa inhibitors. Hematol Oncol Clin North Am. 2010 Aug. 24(4):727-37, viii-ix. [Medline].

Medi C, Hankey GJ, Freedman SB. Stroke risk and antithrombotic strategies in atrial fibrillation. Stroke. 2010 Nov. 41(11):2705-13. [Medline].

Becattini C, Lignani A, Agnelli G. New anticoagulants for the prevention of venous thromboembolism. Drug Des Devel Ther. 2010. 4:49-60. [Medline].

Desai SS, Massad MG, DiDomenico RJ, et al. Recent developments in antithrombotic therapy: will sodium warfarin be a drug of the past?. Recent Pat Cardiovasc Drug Discov. 2006 Nov. 1(3):307-16. [Medline].

Hanley JP. Warfarin reversal. J Clin Pathol. 2004 Nov. 57(11):1132-9. [Medline]. [Full Text].

Keeney M, Allan DS, Lohmann RC, Yee IH. Effect of activated recombinant human factor 7 (Niastase) on laboratory testing of inhibitors of factors VIII and IX. Lab Hematol. 2005. 11(2):118-23. [Medline].

Malherbe S, Tsui BC, Stobart K, Koller J. Argatroban as anticoagulant in cardiopulmonary bypass in an infant and attempted reversal with recombinant activated factor VII. Anesthesiology. 2004 Feb. 100(2):443-5. [Medline].

Powner DJ, Hartwell EA, Hoots WK. Counteracting the effects of anticoagulants and antiplatelet agents during neurosurgical emergencies. Neurosurgery. 2005 Nov. 57(5):823-31; discussion 823-31. [Medline].

Condition

Prevalence in General Population (%)

Relative Risk of VTE (%)

Relative Risk of Recurrent VTE (%)

Factor V Leiden

(heterozygous)

3-7

4.3

1.3

Prothrombin 20210A

(heterozygous)

1-3

1.9

1.4

Protein C deficiency

(heterozygous)

0.02-0.05

11.3

2.5

Protein S deficiency

(heterozygous)

0.01-1

32.4

2.5

Antithrombin deficiency

(heterozygous)

0.02-0.04

17.5

2.5

VTE = Venous thromboembolism

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MBBCh, FRCPC, DTM&H Professor of Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MBBCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Srikanth Nagalla, MBBS, MS, FACP Associate Professor of Medicine, Division of Hematology and Oncology, UT Southwestern Medical Center

Srikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Nothing to disclose.

Pradyumna D Phatak, MBBS, MD Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching.

Barbara P Schick, PhD 

Disclosure: Nothing to disclose.

Hereditary and Acquired Hypercoagulability

Research & References of Hereditary and Acquired Hypercoagulability|A&C Accounting And Tax Services
Source

58 thoughts on “Hereditary and Acquired Hypercoagulability

  1. Pingback: ed pills for sale
  2. Pingback: cheapest ed pills
  3. Pingback: walmart pharmacy
  4. Pingback: Buy cialis online
  5. Pingback: generic levitra
  6. Pingback: vardenafil 10mg
  7. Pingback: casino
  8. Pingback: online slots
  9. Pingback: installment loans
  10. Pingback: installment loans
  11. Pingback: cash loan
  12. Pingback: viagra pills
  13. Pingback: cialis 20
  14. Pingback: generic cialis
  15. Pingback: cialis 20
  16. Pingback: cialis 20
  17. Pingback: casino game
  18. Pingback: casino gambling
  19. Pingback: free slots
  20. Pingback: canada viagra
  21. Pingback: viagra pills
  22. Pingback: cialis buy online
  23. Pingback: casino slots
  24. Pingback: online slots
  25. Pingback: viagra buy
  26. Pingback: Viagra 130 mg otc
  27. Pingback: online viagra
  28. Pingback: rxtrust pharm
  29. Pingback: tamoxifen 10mg usa
  30. Pingback: rx trust pharm
  31. Pingback: RxTrustPharm
  32. Pingback: casino slots
  33. Pingback: Viagra jelly

Leave a Reply