Bleeding Coagulopathies¶

Hayley Hawkins

Bleeding tendency or dysfunction in clot formation can occur from either a quantitative or qualitative platelet defect, deficiency or inhibitor of coagulation factors, or compromise of vascular integrity
Platelet disorders will present with mucocutaneous bleeding, petechiae, mild bleeding immediately following surgery, impaired wound healing
Coagulation defects will present with deep tissue bleeding in joints/muscles resulting in hemarthroses, hematomas, sometimes delayed but severe bleeding after surgery, and intracranial hemorrhage

Qualitative or Quantitative Platelet Defects¶

Most common inherited bleeding disorder, but can be secondary or acquired by other disease states
Three types
- Type 1 (most common): quantitative defect with normal vWF function
- Type 2: qualitative defect with abnormal vWF function despite normal quantity
- Type 3 (rare): complete absence of vWF, phenotypically similar to hemophilia A (vWF forms complex with factor VIII)
Causes of acquired vWD
- Lymphoproliferative disorders: CLL, NHL, plasma cell dyscrasias
- Myeloproliferative disorders: PV, ET, or myelofibrosis
- Autoimmune diseases: SLE
- Sheer stress: aortic stenosis – Heidi syndrome, LVAD, ECMO
- Hypothyroidism
Diagnosis:
- “vW Profile” = vWF Ag, Factor VIII Activity, Ristocetin Cofactor Activity
Management:
- Major bleeding or major surgery: give VFW concentrate (some formulations have FVIII)
- Minor bleeding or surgery or prophylaxis: DDAVP, TXA or aminocaproic acid in some circumstances

Uremic platelet dysfunction
Medications: NSAIDs, anti-platelets (ASA, Plavix), SSRIs (serotonin required for platelet activation), and melatonin (suggested by pre-clinical studies)

X-linked recessive inheritance
Frequently presents with hemarthroses and hematomas
Diagnosis: Isolated prolonged PTT with normalization upon mixing study
Management: Purified/recombinant Factor VIII or IX, mild disease can be managed with desmopressin, consult Benign Hematology on admission

Onset in older age (60s) and frequently presents with significant intramuscular hematomas
Disease associations in 50% of cases (other 50% idiopathic): autoimmune (e.g. SLE), malignancy (paraneoplastic), Pemphigus, drug-induced (e.g. interferon, penicillins), or chronic GvHD
Diagnosis: Elevated PTT that does not normalize with mixing study
Management:
- Always consult Hematology (rare disorder with major bleeding complications)
- Bleeding: Typically need a factor VIII bypassing agent (FEIBA)
- Immunosuppression: prednisone 1mg/kg, rituximab often also used front line

Factor VIII deficiency: see vWD above
Vitamin K deficiency
- Caused by malnutrition, liver disease (biliary obstruction), or iatrogenic with warfarin
- Diagnosis: elevated PT, prolonged PTT if severe, hepatic function panel
- Management: IV vitamin K 10mg x 3 days
DIC and liver dysfunction/cirrhosis
- A FVIII level can help distinguish between the two (elevated or normal in liver dysfunction and decreased in DIC since it is not hepatically derived)
Amyloidosis: can cause factor X deficiency
Medications: warfarin, DOACs

Amyloidosis: can present as GI bleeding, purpura or ecchymoses (e.g. Raccoon eyes)
Vasculitis: purpura, alveolar hemorrhage (DAH), intracranial hemorrhage, GI bleeding
Vitamin C deficiency: can present with bleeding gums, GI bleeding, ecchymoses, hematomas, anemia
AVMs (fragile vessels that easily bleed)
Hereditary hemorrhagic Telangiectasia
- 2^nd most common inherited bleeding disorder
- Often presents with epistaxis, GI bleeding
- AVMs found in GI tract, lung (may cause shunting), liver (can contribute to cirrhosis), brain
vWD
- von Willebrand multimers play direct role in modulating angiogenesis
Heidi Syndrome: acquired vWD due to aortic stenosis, presents with GI bleeding from AVMs