03 Acquired Hemostatic Defects Flashcards
Causes of Qualitative Platelet Disorders?
- Failure of production
- Leukemia
- Myeloproliferative disorders
- B12 or folate deficiencies
- ChemoRT
- Acute alcohol intoxication
- Viral infections - Decreased survival
- Immune-mediated (ITP, HIT, Autoimmune,secondary)
- DIC
- Platelet thrombi (TTP, HUS) - Sequestration
- Portal HTN
- Sarcoid
- Lymphoma
- Gaucher’s Disease
Causes of Qualitative Platelet Disorders?
- Massive transfusion
- Therapeutic platelet inhibitors
- Disease states
- Myeloproliferative disorders
- Monoclonal gammopathies
- Liver disease
Symptoms of secondary immune thrombocytopenia?
Very low platelet count
Petechia
Purpura
Epistaxis
Laboratory findings of secondary immune thrombocytopenia?
Large platelets on peripheral smear
Treatment of secondary immune thrombocytopenia?
Initial:
Corticosteroids
IVIG
Anti-D immunoglobulin
Indications for platelet transfusion in secondary immune thrombocytopenia?
CNS bleeding
Active bleeding from other sites
Survival of transfused platelets is usually short.
Symptomatology of primary immune thrombocytopenia or ITP?
Children: Acute, short-lived, viral
Adults: Gradual, chronic, no identifiable cause
Pathophysiology of ITP?
- Impaired platelet production
2. T-cell mediated platelet destruction
Pathophysiology of HIT?
Antibodies against platelet factor 4 (PF4) formed during exposure to heparin affect platelet activation and endothelial function, resulting in thrombocytopenia and intravascular thrombosis.
Signs of HIT?
Platelet count begins to fall 5-7 days after heparin has been started, but may occur within 1-2 days if it is a re-exposure.
HIT should be suspected if platelet count falls to <100,000 or drops by 50% from baseline in a patient receiving heparin.
In what kind of heparin is HIT more common?
HIT is more common in full-dose unfractionated heparin. However, it can also occur with prophylactic doses of LMW heparins.
How is HIT diagnosed?
- Serotonin-release assay (SRA)
- Highly specific, but NOT sensitive. A positive test supports HIT, but a negative test does not exclude HIT. - Enzyme-linked immunosorbent assay (ELISA)
- Low specificity
- A positive ELISA confirms presence of anti-heparin PF4, but does not help diagnose clinical HIT. A negative ELISA rules out HIT.
Initial treatment of suspected HIT?
Stop heparin, and begin an alternative anticoagulant.
Alternative anticoagulants to heparin in HIT?
Thrombin inhibitors
- Normal renal function: Lepirudin, argatroban, danaparoid
- Renal insufficiency: Argatroban
When should warfarin be started in patients with HIT?
Only once full anticoagulation with an alternative agent has been accomplished, and the platelet count has begun to recover.
Pathophysiology of thrombotic thrombocytopenic purpura?
Large vWF molecules interact with platelets, leading to activation.
The large molecules result from inhibition of a metalloproteinase enzyme, ADAMtS13, which cleaves the large vWF molecules.
Signs and symptoms of TTP?
Thrombocytopenia Microangiopathic hemolytic anemia Fever Renal/Neurologic Sx and Ssx PBS: +Schistocytes
Treatment or Acute TTP?
Plasma exchange with replacement of FFP
Rituximab (monoclonal antibody against CD20 protein)
Etiology of Hemolytic Uremic Syndrome (HUS)?
Infection with E. Coli 0157:H7 or other Shiga toxin-producing bacteria
Symptoms of HUS?
Renal failure, with some requiring RRT
Normal metalloproteinase
Conditions in which both HUS and TTP features are present?
Autoimmune disease (SLE, HIV) Drug-induced (Ticlopidine, Mitomycin C, Gemcitabine) Immunosuppressive agents (Cyclosporine, Tacrolimus)
Treatment of HUS?
Discontinue involved drug
Plasmapheresis
Pathophysiology of thrombocytopenia caused by sequestration?
Trapping of platelets in an enlarged spleen, related to portal hypertension, Sarcoid, lymphoma or Gaucher’s disease.
The total body platelet mass is essentially normal in patients with hypersplenism, but a much larger fraction of the platelets are in the enlarged spleen.
