Hematology and Oncology Book

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Hypercoagulable

Aka: Hypercoagulable, Hypercoagulability, Thrombophilia
  1. See Also
    1. Recurrent Venous Thromboembolism Risk
    2. Pulmonary Embolism
    3. Deep Vein Thrombosis
  2. History: Findings suggestive of Hypercoagulable State
    1. Thrombosis at a young age (age under 50 years)
    2. Family History of thrombosis
    3. Recurrent Thrombosis
    4. Thrombosis in an unusual site (hepatic, mesenteric, or cerebral)
    5. Pregnancies complicated by frequent Miscarriage or IUGR
    6. Idiopathic venous thrombembolism or unprovoked VTE (No known predisposing factors)
  3. Etiologies: Primary Hypercoagulable States (Hereditary)
    1. Common Causes
      1. Factor V Leiden Defect
      2. Prothrombin 20210
      3. Homocystinuria or Hyperhomocysteinemia
    2. Uncommon Causes
      1. Antithrombin III deficiency
      2. Protein C Deficiency
      3. Protein S Deficiency
      4. Factor VIII Increased
      5. Fibrinolysis
      6. Dysfibrinogenemia
  4. Etiologies: Secondary or Acquired Hypercoagulable States
    1. Antiphospholipid Antibody Syndrome (most common)
    2. Pregnancy
    3. Surgery
    4. Trauma
    5. Infection or Sepsis
    6. Malignancy
      1. Cancer in idiopathic Hypercoagulability with unprovoked VTE: 3.9% (as high as 20% in some studies)
        1. Carrier (2015) N Engl J Med 373(8): 697-704 [PubMed]
      2. Basic evaluation for occult malignancy
        1. Standard interval HME screening is appropriate (e.g. Pap Smear, Mammogram, Colonoscopy)
        2. However CT Abdomen and Pelvis is not recommended for unprovoked VTE alone
          1. Carrier (2015) N Engl J Med 373(8): 697-704 [PubMed]
    7. Medications
      1. Estrogen sources
        1. Oral Contraceptives
        2. Estrogen Replacement Therapy
        3. Tamoxifen
      2. Hydralazine
      3. Phenothiazines
      4. Procainamide
    8. Myeloproliferative disorder
    9. Hyperlipidemia
    10. Homocystinuria
    11. Lupus Inhibitor
    12. Nephrotic Syndrome
  5. Labs: Indications for testing based on level of suspicion
    1. General
      1. Hold blood for tests below before Anticoagulation
    2. Risk of Thrombophilia determines level of testing
      1. Unlikely to be thrombophilic
        1. Criteria
          1. First episode of Venous Thromboembolism and
          2. Known Thromboembolism Risk Factors and
          3. No Family History of Thromboembolism
            1. No first degree relative under age 50 years
        2. Testing
          1. No testing indicated
      2. Weakly thrombophilic
        1. Criteria
          1. Age over 50 years and
          2. First thromboembolic episode and
            1. No known Thromboembolism Risk Factors
          3. No Family History of Thromboembolism
            1. No first degree relative under age 50 years
        2. Testing
          1. Evaluation of common causes (see below)
      3. Strongly thrombophilic
        1. Criteria
          1. Age <50, no known Thromboembolism Risk Factors or
          2. Recurrent thromboembolic episode or
          3. Family History of Thromboembolism
            1. First degree relative under age 50 years
        2. Testing
          1. Evaluation of common causes and
          2. Evaluation of less common causes (see below)
  6. Labs: Evaluation of common causes ($250)
    1. Complete Blood Count with platelets and morphology
    2. Prothrombin Time
    3. Partial Thromboplastin Time
      1. Lupus Anticoagulant Syndrome suspected if increased PTT that does not correct with 1:1 dilution with normal plasma
    4. Connective Tissue Disorder tests
      1. Antinuclear Antibody Test (ANA)
      2. Antiphospholipid Antibody tests
        1. Clotting Assay for Lupus Anticoagulant (affected by Anticoagulants)
        2. ELISA for Anticardiolipin Antibodies
        3. B2 Glycoprotein Antibody may ultimately replace these tests as it has higher Specificity
        4. Test 3-4 weeks after Anticoagulation and acute event resolved and then repeat for confirmation in 12 weeks
    5. Factor V Leiden or APC Resistance (G1681A)
      1. Initial: Clotting based assay
      2. Confirmatory: Factor V Leiden
    6. Factor II Prothrombin Mutation Analysis (G20210A)
    7. Fasting Total Plasma Homocysteine Level
      1. Controversial as whether to check as the significance is questionable
      2. If high then check C677T as follows:
      3. Methylenetetrahydrofolate reductase (C677T)
  7. Labs: Evaluation of less common causes ($900)
    1. General
      1. Indicated for strongly thrombophilic patients
      2. Testing includes all labs above
      3. Obtain lab testing 2 weeks after off Anticoagulants
      4. These conditions are highly thrombophilic
    2. Protein C Levels and Protein S Levels
      1. Antigenic (total protein) and functional levels
    3. Antithrombin III Level (HeparinCofactor assay)
    4. Plasma Factor VIII Level (increased)
  8. Management
    1. High Risk Indications for life-long Anticoagulation
      1. Two or more spontaneous thrombotic events
      2. One spontaneous life-threatening event
      3. One spontaneous event with high risk cause
        1. Antiphospholipid Syndrome
        2. Antithrombin III deficiency
        3. More than one inherited abnormality
    2. Moderate Risk Indications for event-based prophylaxis
      1. One event with known provocative stimulus
  9. Resources
    1. University of Illinois Carle Cancer Center Resources
      1. http://www.med.uiuc.edu/hematology/index.htm
  10. References
    1. Bauer (2001) Ann Intern Med 135:367-73 [PubMed]
    2. Harris (1997) Am Fam Physician 56(6):1591-6 [PubMed]
    3. Kyrle (2000) N Engl J Med 343:457-62 [PubMed]
    4. Nachman (1996) Ann Intern Med 119:819-27 [PubMed]
    5. Thomas (1997) Ann Intern Med 126:638-44 [PubMed]

Thrombophilia (C0398623)

Definition (NCI) A condition characterized by an abnormally high level of thrombi. Causes include thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, bone marrow disorders, and antiphospholipid antibody syndrome.
Definition (MSH) A disorder of HEMOSTASIS in which there is a tendency for the occurrence of THROMBOSIS.
Concepts Disease or Syndrome (T047)
MSH D019851
ICD10 D68.59
SnomedCT 191302007, 76612001, 234467004
English Hypercoagulability, Hypercoagulabilities, Thrombophilias, thrombophilia (diagnosis), thrombophilia, Excessive Blood Clotting, Hypercoagulable state NOS, Thrombophilia NOS, Thrombophilia [Disease/Finding], thrombophilias, hypercoagulable state, hypercoagulability states, hypercoagulability, hypercoagulable states, Thrombophilia, Hypercoagulability State, Hypercoagulability state, Hypercoagulable state, Hypercoagulability state (finding), Thrombophilia (disorder), Hypercoagulability state, NOS
Dutch trombofilie, Hypercoagulabiliteit, Trombofilie
Japanese 栓友病, センユウビョウ, 血栓形成傾向, 血栓傾向
Swedish Trombofili
Czech trombofilie, Trombofilie
Finnish Trombofilia
Russian TROMBOFILIIA, ТРОМБОФИЛИЯ
Italian Ipercoagulabilità, Trombofilia
Polish Trombofilia, Nadkrzepliwość
Hungarian Thrombophilia
Croatian TROMBOFILIJA
Norwegian Hyperkoagulasjon, Trombofili, Trombosetendens
Spanish estado de hipercoagulabilidad (hallazgo), estado de hipercoagulabilidad, estado hipercoagulable, hipercoagulabilidad, trombofilia (trastorno), trombofilia, Trombofilia, Hipercoagulabilidad
French Thrombophilie, Hypercoagulabilité
German Thrombophilie, Hyperkoagulabilität
Portuguese Hipercoagulabilidade, Trombofilia
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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