Pocket Oncology (Pocket Notebook Series), 1st Ed.

BLEEDING DIATHESES

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.