Melody Smith and Gerald A. Soff
Definition:
• Spontaneous, excessive, or delayed bleeding following tissue injury
• Localized pathologic process
• Disorders of vascular integrity/function
• Disorders of plt number and/or function
• Disorders of coagulation factors, hereditary vs. acquired.
• ↑fibrinolysis
Initial Evaluation
• Obtain pt’s bleeding hx, FHx, medication use, & perform PEx
• Initial tests:
• PT,
• Activated partial thromboplastin time (aPTT),
• Fibrinogen
• CBC
Disorders of Blood Vessels
• Bleeding or bruising may result from blood vessels that are not formed properly or do not function properly
• Genetic
• Hemorrhagic telangiectasia: (Osler–Weber–Rendu syndrome), AD inheritance. Fragile vascular telangiectasias result in recurrent episodes of bleeding, particularly GI & oral-pharyngeal.
• Ehlers–Danlos syndrome: Defect in collagen synthesis resulting in weak, elastic collagen w/in blood vessels that causes them to be more prone to injury. May be AD or AR inheritance depending on type of Ehler–Danlos syndrome
• Acquired
• Allergic, infectious, renal insufficiency, chronic glucocorticoids, vitamin C deficiency (scurvy).
Platelet Disorders
• Quantitative (NEJM 2008;359:1261):
• ITP-↑plt destruction (± inhibition of plt production) via the production of specific autoantibodies
• Drug-induced thrombocytopenia: Variable mechanisms
• Other causes: Sepsis, cirrhosis, aplastic anemia, DIC
• Qualitative:
• Inherited:
• Glanzmann thrombasthenia – Defective plt aggregation (Deficiency of GPIIb/IIIa)
• Bernard–Soulier syndrome – Defective plt adhesion (Deficiency of von Willebrand Receptor/Gp Ib/V/IX)
• Storage-pool Disease – Defective plt granule release.
• Acquired: Uremia, myelodysplastic syndrome, medications
Diagnostic Approach:
• CBC, peripheral smear, coagulation studies (PT, PTT), fibrinogen, plt function, mixing studies for inhibitor. Specific factor levels based on initial PT, PTT.
Coagulation Factor Deficiency or Dysfunction
• Inherited:
• vWD: Different types, most AD. Sev. / (Type III AR). ↓ production or dysfunction of vW factor resulting in reduced plt adherence to the injured blood vessel & ↑ blood loss (NEJM 2004;351:683)
• Hemophilia A (↓ FVIII) & B (↓ FIX): X-linked recessive. Delayed bleeding, deep muscle bleeds. Hemarthrosis (joint bleeds) most common event. Managed w/Factor Concentrate replacement.
• Factor XI Deficiency. AR. More common among AJ.
• Acquired: Liver disease (NEJM 2011;365:147), Vitamin K deficiency, DIC, liver dysfunction, acquired factor inhibitors, anticoagulant medications
Diagnostic Approach to Systemic Coagulopathy
Excessive Fibrinolysis
• Characterized by excessive fibrinolysis due to an inherited or acquired excess of a plasminogen activator inhibitor. Some cases of PC, acute promyelocytic leukemia
Clinical Manifestations
• 1° Hemostasis (plt/vascular): Typically, mucocutaneous bleeding. Petechiae, menorrhagia, ecchymoses, purpura, unexplained easy bruising immediate.
• 2° Hemostasis (Factor deficiency): Often delayed. Organ, muscle, intracranial, or joint bleeds.
Treatment
• ITP: Acute: IVIG, glucocorticoids. Chronic: Rituximab, splenectomy, Tpo receptor agonists.
• Thrombocytopenia, Drug-induced: Remove inciting drugs. May support w/transfusions.
• Renal Insufficiency: EPO or transfusion to ↑ Hgb to ≥10 g/dL. DDAVP for acute.
• vWD: DDAVP for minor bleeds, minor surgery. Humate-P (Factor concentrate w/vW Protein) for major bleeds/surgery. Type IIb vWD may have detrimental response to DDAVP causing thrombocytopenia, need to r/o type IIB before use or test dose.
• Hemophilia A, B. Specific factor concentrates
• Factor VIII: 1 unit/kg → 2% ↑ in level. Twice daily
• Factor IX concentrate: 1 unit/kg → 1% ↑ in level. Once daily
• Factor XI Deficiency: Plasma infusion. Usu 2–3 units are sufficient for surgery or major bleeds.