03 Acquired Hemostatic Defects

Question 1

Causes of Qualitative Platelet Disorders?

Answer 1

1. Failure of production
   - Leukemia
   - Myeloproliferative disorders
   - B12 or folate deficiencies
   - ChemoRT
   - Acute alcohol intoxication
   - Viral infections
2. Decreased survival
   - Immune-mediated (ITP, HIT, Autoimmune,secondary)
   - DIC
   - Platelet thrombi (TTP, HUS)
3. Sequestration
   - Portal HTN
   - Sarcoid
   - Lymphoma
   - Gaucher’s Disease

Question 2

Causes of Qualitative Platelet Disorders?

Answer 2

1. Massive transfusion
2. Therapeutic platelet inhibitors
3. Disease states
   - Myeloproliferative disorders
   - Monoclonal gammopathies
   - Liver disease

Question 3

Symptoms of secondary immune thrombocytopenia?

Answer 3

Very low platelet count
Petechia
Purpura
Epistaxis

Question 4

Laboratory findings of secondary immune thrombocytopenia?

Answer 4

Large platelets on peripheral smear

Question 5

Treatment of secondary immune thrombocytopenia?

Answer 5

Initial:
Corticosteroids
IVIG
Anti-D immunoglobulin

Question 6

Indications for platelet transfusion in secondary immune thrombocytopenia?

Answer 6

CNS bleeding
Active bleeding from other sites

Survival of transfused platelets is usually short.

Question 7

Symptomatology of primary immune thrombocytopenia or ITP?

Answer 7

Children: Acute, short-lived, viral

Adults: Gradual, chronic, no identifiable cause

Question 8

Pathophysiology of ITP?

Answer 8

1. Impaired platelet production

2. T-cell mediated platelet destruction

Question 9

Pathophysiology of HIT?

Answer 9

Antibodies against platelet factor 4 (PF4) formed during exposure to heparin affect platelet activation and endothelial function, resulting in thrombocytopenia and intravascular thrombosis.

Question 10

Signs of HIT?

Answer 10

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.

Question 11

In what kind of heparin is HIT more common?

Answer 11

HIT is more common in full-dose unfractionated heparin. However, it can also occur with prophylactic doses of LMW heparins.

Question 12

How is HIT diagnosed?

Answer 12

1. Serotonin-release assay (SRA)
   - Highly specific, but NOT sensitive. A positive test supports HIT, but a negative test does not exclude HIT.
2. 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.

Question 13

Initial treatment of suspected HIT?

Answer 13

Stop heparin, and begin an alternative anticoagulant.

Question 14

Alternative anticoagulants to heparin in HIT?

Answer 14

Thrombin inhibitors

• Normal renal function: Lepirudin, argatroban, danaparoid
• Renal insufficiency: Argatroban

Question 15

When should warfarin be started in patients with HIT?

Answer 15

Only once full anticoagulation with an alternative agent has been accomplished, and the platelet count has begun to recover.

Question 16

Pathophysiology of thrombotic thrombocytopenic purpura?

Answer 16

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.

Question 17

Signs and symptoms of TTP?

Answer 17

Thrombocytopenia
Microangiopathic hemolytic anemia
Fever
Renal/Neurologic Sx and Ssx
PBS: +Schistocytes

Question 18

Treatment or Acute TTP?

Answer 18

Plasma exchange with replacement of FFP

Rituximab (monoclonal antibody against CD20 protein)

Question 19

Etiology of Hemolytic Uremic Syndrome (HUS)?

Answer 19

Infection with E. Coli 0157:H7 or other Shiga toxin-producing bacteria

Question 20

Symptoms of HUS?

Answer 20

Renal failure, with some requiring RRT

Normal metalloproteinase

Question 21

Conditions in which both HUS and TTP features are present?

Answer 21

Autoimmune disease (SLE, HIV)
Drug-induced (Ticlopidine, Mitomycin C, Gemcitabine)
Immunosuppressive agents (Cyclosporine, Tacrolimus)

Question 22

Treatment of HUS?

Answer 22

Discontinue involved drug

Plasmapheresis

Question 23

Pathophysiology of thrombocytopenia caused by sequestration?

Answer 23

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.