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Hypercoagulability Differential Diagnosis                                                                                                      

1. Malignancy

• 5-15% tumors overall
• Nearly 50% of patients with pancreatic cancers have some thromboembolic event
• May be due to activation of platelets by tumors and/or production of procoagulants
• May also be related to interference with protein S (or C) function
• Migratory thrombophlebitis (Trousseau's Syndrome) not uncommon

2. Pregnancy

3. Oral contraceptives (usually with smoking or other hypercoagulable state)

4. Nephrotic syndrome

• Loss of fibrinolytic components (eg. antithrombin III, proteins C or S) through filtration
• Check albumin levels; urine:serum albumin ratio.

5. Myeloproliferative Disorders

6. Hyperlipidemias

7. Diabetes mellitus

8. Paroxysmal nocturnal hemoglobinuria (PNH): abnormal platelet membrane

9. Immobilization

10. Postoperative (immobilization, bed rest)      Back to top |   Home Page

11. Vasculitis and Collagen Vascular Disease

• SLE "Lupus Anticoagulant"
• Anti-phospholipid Syndrome
• Thromboangiitis obliterans
• ANCA Associated Vasculitis
• Cryoglobulinemia

12. Hyperviscosity syndromes

• Sickle Cell Anemia
• Polycythemia
• Hypergammaglobulinemia (esp IgM)

13. Deficiency/Dysfunction of Anticoagulants

• Antithrombin III - absence, reduction, resistance
• Protein C - deficiency may be accompanied by DIC
• Resistance to activated protein C (usually Factor V mutation)
• Protein S
• Must check liver function, vitamin K levels (Proteins C and S are Vitamin K dependent)
• Protein C or S deficiency symptoms may be precipitated by use of Warfarin without heparin

14. Homocystinemia and Homocysteinuria

• High homocysteine levels are a mild to severe risk factor for premature vascular disease
• Risk factor for arterial > venous thromboemboli - early MI not uncommon
• Genetic disease (homzygous cystathionine ß-synthase deficiency) - severe events
• Also includes mental retardation, ectopia lentis, skeletal abnormalities (osteoporosis)

15. Heparin-Induced Thrombocytopenia (antibody mediated)      Back to top |   Home Page

16. Anti-Neoplastic agents (vascular endothelial damage; HUS/TTP)

17. Obesity

18. Clotting Pathways

• Increased Levels of plasma Factor VII and/or Fibrinogen
• Factor VII Genotype H6H6

19. Smoking (usually exacerbates underlying hypercoagulable state)

20. Combinations of hypercoagulation risks are additive or synergistic

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References:  
Outlines in Clinical Medicine on Physicians' Online   2000   
E-Medicine  Hyperviscosity Syndrome 
Nachman RL and Silverstein R. 1993. Ann Intern Med. 119(8):819
Fermo I, D'Angelo V, Paroni R, et al. 1995. Ann Intern Med. 123(10):747
van der Bom JG, Bots ML, Haverkate F, et al. 1996. Ann Intern Med. 125(4):265
Price DT and Ridker PM. 1997. Ann Intern Med. 127(10):895
Iacoviello L, Di Castelnuovo A, de Knijff P, et al. 1998. NEJM. 338(2):79

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07172002

See Hypercoagulable Disorder Review (Arch IM April 23, 2001)

Anticardiolipin Antibodies (ACA)
belong to the antiphospholipid antibody group of proteins & may have anticoagulant activity (similar to that of lupus anticoagulants)

The antiphospholipid antibody syndrome
is characterized by recurrent clinical events: noninflammatory thrombosis of small or large arteries and/or veins & fetal loss, with demonstrable antiphospholiid antibodies (anticardiolipin antibody or lupus anticoagulant).  The syndrome is primary if SLE is not present.