Platelets -H/O

Question 1

Mechanisms of Thrombocytopenia

Answer 1

1. Decreased Production
   - Bone marrow failure (aplastic anemia, MDS, inherited marrow failure states)
   - Marrow replacement (leukemia, lymphoma, metabolic disorders)
   - Marrow toxins (drugs, radiation, ethanol)
   - Nutritional deficiency (B12, folic acid)
2. Increased Destruction / Consumption
   - Immunologic (drugs, HIT, ITP)
   - Non Immunologic (DIC, TTP/HUS)
3. Hypersplenism

Question 2

Drug Induced Thrombocytopenia

Answer 2

-can directly affect the marrow
OR
-can have antibodies directed against drug/platelet complex or drug induced antibody response
Tx-stop offending drug

Question 3

HIT

Answer 3

• Immune response directed against heparin / platelet factor 4 complexes
• Anti-Hep/PF4 IgG binds to platelet Fc receptors, resulting in platelet activation and generation of microparticles and thrombin
• Thrombocytopenia begins 5 - 10 days after initiation of heparin exposure (may occur sooner in patients with recent exposure and residual antibodies)
• More than 50% decrease from baseline platelet count or absolute thrombocytopenia
• Absence of other causes of thrombocytopenia
• ANY form of heparin can precipitate HIT (although less common with low MW heparins)
• Confirmation by lab testing
• Return to normal platelet count when heparin is discontinued
• Venous and / or arterial thrombosis occurs in 30 - 50% - 10% require limb amputation, 20% mortality

Question 4

Immune Thrombocytopenic Purpura (ITP)

Answer 4

• Loss of tolerance to self
• IGG antibody against glycoprotein IIb/IIIa, Ib/IX
• Cytokines, abnormal T cells…
• Autoantibodies that bind to platelets and accelerate their clearance by the spleen
• ITP is a diagnosis of exclusion
• Most common cause of thrombocytopenia in childhood, adolescence and young adults

Childhood ITP:
-Acute onset, often after viral illness
-Often resolves spontaneously within days or weeks
>90% resolve 1-2 years after dx

Adult ITP:

• Insidious onset (most have symptoms for > 2 months)
• Rarely resolves spontaneously
• May patients go on to have chronic ITP

Question 5

Clinical Features of ITP

Answer 5

• Most adults have symptoms for > 2 months, children have symptoms for a day or two
• Most children have no associated health issues
• Most adults have other associated medical issues – autoimmune disorders, malignancy, etc.
• Petechiae in dependent regions
• Echymosis
• Menorrhagia, epistaxis, gingival bleeding, blood in stool or urine
• Otherwise healthy
• No lymphadenopathy or splenomegaly

Question 6

Laboratory Features of ITP

Answer 6

• Severe thrombocytopenia (platelets < 10,000)
• In adults or in patients with more insidious onset platelet count may be in range of 20-60,000.
• CBC otherwise normal, MPV high
• Peripheral smear may show large platelets
• Normal coagulation times (PT/INR, PTT) and fibrinogen
• Normal/increased megakaryocytes in bone marrow
• Platelet antibody tests are rarely helpful

Question 7

Treatment of ITP

Answer 7

ADULTS

1. Steroids
2. IVIG
3. WinRho
4. Rituxan
5. Splenectomy
6. Observation

Children

1. Observation – 75%
2. IVIG
3. WinRho
4. Steroids
5. Rituxan
6. Splenectomy

Question 8

Disseminated Intravascular Coagulation

DIC

Answer 8

• Life-threatening coagulation disorder caused by excessive activation of coagulation system that overwhelms natural anticoagulant mechanisms
• Microvascular thrombi cause widespread tissue ischemia and multiple organ dysfunction
• Bleeding due to consumption of platelets and plasma clotting factors
• Thrombocytopenia
• Prolonged coagulation times (PT/INR, PTT)
• Low fibrinogen, other coagulation factors also low
• Schistocytes on blood smear
• VERY ILL appearing

Question 9

Disseminated Intravascular Coagulation

(DIC) - causes/tx

Answer 9

Causes
-Infection / sepsis
-Malignancy
-Obstetrical catastrophes (abruption placenta, amniotic fluid embolism, retained tissue)
-Severe tissue injury (trauma, burns)
Tx
-Treat the underlying cause
-Transfuse platelets, FFP, cryoprecipitate as needed
-Consider low dose heparin

Question 10

Classification of thrombotic thrombocytopenic purpura (TTP)

Answer 10

1. Idiopathic
2. Secondary
   - Pregnancy
   - Autoimmune disease (SLE, scleroderma)
   - Drug toxicity (chemotherapy, CSA, ticlopidine)
   - HIV infection
   - Bone marrow transplant
   - Malignancy
3. Familial

Question 11

Classic Pentad of TTP

Answer 11

1. Thrombocytopenia
2. Microangiopathic hemolytic anemia
3. Neurologic symptoms
4. Renal dysfunction
5. Fever
   - If you wait for the entire pentad to develop, you have waited too long !

Question 12

Diagnosis of TTP

Answer 12

1. High index of clinical suspicion
2. Hemolysis + Thrombocytopenia = TTP, DIC…
3. Coagulation times should be normal, or only slightly prolonged
4. Examination of the peripheral blood smear is absolutely essential !
5. ADAMST 13 level

Question 13

Treatment of TTP

Answer 13

• Treatment must be started promptly
• Plasma exchange has been the main treatment modality since the early 1980s
• Prior to the use of plasma exchange, the mortality rate for TTP was 90%
• With prompt diagnosis and treatment, 90% of patients now survive

Question 14

Hemolytic uremic syndrome

Answer 14

• Seen primarily in children
• Predominantly renal symptoms, anemia and thrombocytopenia
• Associated with infections with E coli or Shigella dysenteriae
• Patients often require dialysis
• Therapy is generally supportive

Question 15

HIT summary

Answer 15

• Heparin exposure
• Platelets drop more than 50% from baseline
• Variable INR, PTT, Fibrinogen
• Life- and limb-threatening

Question 16

ITP summary

Answer 16

• Healthy
• Severe thrombocytopenia, CBC otherwise normal
• Normal INR, PTT, Fibrinogen
• Rarely life-threatening

Question 17

DIC summary

Answer 17

• Sick, bleeding > thrombosis
• Falling platelets
• Prolonged INR, PTT, low fibrinogen
• Treat the underlying cause

Question 18

TTP / HUS

Answer 18

• Sick, bleeding and thrombosis, CNS, renal
• Falling platelets, MAHA
• Normal INR, PTT, fibrinogen
• 90% fatal if unrecognized and untreated