Thrombocytopenia

Question 1

A platelet count of <100,000/μL generally defines (1). (2)

usually does not occur until counts are <50,000/μL .Platelet counts <20,000/μL are associated with

(3), and <10,000 with (4)

Answer 1

1. thrombocytopenia 2. Hemorrhage from minor trauma 3. spontaneous (i.e. non traumatic) bleeding 4. risk of spontaneous intracerebral hemorrhage

Question 2

Generally spontaneous bleeding involves ?

Answer 2

small blood vessels, skin, and mucosal membranes of the GI or GU tract

Question 3

What are the general causes of thrombocytopenia?

Answer 3

1. Decreased platelet production 2. Decreased platelet survival 3. Splenic sequestration 4. Dilution thrombocytopenia

Question 4

Decreased platelet production is due to conditions affecting (1) production of platelets or those that directly affect (2) function

Answer 4

1. marrow 2. megakaryocyte

Question 5

Common causes of decreased platelet production include what drugs?

Answer 5

drugs such as alcohol, thiazide diuretics and cytotoxic chemotherapy agents

Question 6

Bone marrow failure as in (1) causes severe thrombocytopenia as does replacement of bone marrow by tumor (2).

Answer 6

1. aplastic anemia 2. leukemia or metastatic tumor involving bone marrow

Question 7

Viral infections such as (1) directly infect (2) causing decreased platelet production.

Answer 7

1. HIV and measles 2. megakaryocytes

Question 8

Common causes of decreased platelet production include?

Answer 8

Drugs - etOH, thiazide diuretics, cytotoxic chemotherapy agents; Aplastic anemia; Leukemia; Metastatic tumor involving bone marrow; Viral infections - HIV, measles; Myelodysplasia; Vit B12 and folate deficiency

Question 9

Decreased platelet survival may be due to what immune causes?

Answer 9

acute or chronic immune thrombocytopenia Infection or drug induced secondary autoimmune Autoimmune disease: SLE, B cell lymphoma, post-transfusion and neonatal isoimmune thrombocytopenia

Question 10

(1) may induce secondary autoimmune thrombocytopenia as may certain infections (2)

Answer 10

1. Quinidine, heparin, vancomycin and sulfa drugs 2. HIV and mononucleosis

Question 11

Non immune mediated causes of decreased platelet survival include (1)

Answer 11

1. DIC, the thrombotic microangiopathies like TTP and HUS

Question 12

What conditions are associated with hypersplenism leading to splenic sequestration and thrombocytopenia?

Answer 12

liver disease portal hypertension CHF mononucleosis Myeloproliferative neoplasms Myelofibrosis

Question 13

caused by (1) autoantibodies usually directed against (2). These autoantibodies are recognized by (3) receptors on (4) with destruction of the platelets occurring in the (5)

Answer 13

1. IgG 2. platelet glycoproteins IIb‐IIIa 3. IgG Fc or opsonins 4. macrophages 5. spleen refers to ITP Chronic Immune Thrombo-cytopenia

Question 14

Chronic ITP may be primary or secondary and associated with entities such as?

Answer 14

HIV; SLE; chronic lymphocytic leukemia

Question 15

S/S of chronic ITP

Answer 15

skin or mucous membrane petechiae or ecchymosis; excessive menstrual bleeding; frequent nosebleeds; melena; *Head trauma in this patient can result in intracranial bleeding”

Question 16

Treatment for chronic ITP

Answer 16

steroids or splenectomy

Question 17

How is acute ITP different from chronic ITP?

Answer 17

Chronic ITP tends to affect women in their 40s, whereas acute ITP tends to affect children following a recent viral infection. Acute ITP is self-limiting, normally resolves within 6 months but 20% of cases progress to chronic ITP.

Question 18

About 5% of patients on (1) experience a form of immune thrombocytopenia with many with serious consequences

Answer 18

1. heparin

Question 19

Heparin binds (1), resulting in a neo‐antigen that stimulates the production of antibody. This process induces (2) and results in (3)

Answer 19

1. platelet factor 4 2. platelet activation 3. thrombosis and thrombocytopenia as platelets are consumed

Question 20

How long does it take HIT to occur?

Answer 20

Generally platelet counts begin to drop 5‐10 days after heparin therapy is started.

Question 21

All patients starting on heparin should have a (1) prior to initiation of heparin therapy.

Answer 21

1. platelet count

Question 22

A drop in platelet count of (1)% or more from baseline is highly suspicious for HIT and if noted, heparin must be discontinued and the patient placed on (2) (this greatly lowers the risk of HIT but does not completely eliminate it!).

Answer 22

1. 50% 2. low molecular weight heparin

Question 23

If HIT goes unrecognized and heparin therapy not stopped the patient may experience extensive arterial thrombotic episodes resulting in ?

Answer 23

vascular insufficiency to limbs, DVT and pulmonary thromboembolism

Question 24

Other drugs such as (1) can bind platelet glycoproteins and induce an antibody response resulting in thrombocytopenia but not (2) as in HIT.

Answer 24

1. quinine, quinidine and vancomycin 2. thrombosis

Question 25

quinine, quinidine and vancomycin

Answer 25

can cause thrombocytopenia but not thrombosis

Question 26

TTP vs. HUS symptoms

Answer 26

both: thrombocytopenia, microangiopathic hemolytic anemia, renal failure, neurologic symptoms (may or may not occur in HUS) TTP: fever HUS: children; bloody diarrhea

Question 27

results from deficiency of ADAMS13 (also called vWf metalloprotease)

Answer 27

TTP

Question 28

enzyme responsible for (1) of high molecular weight multimers of vWf

Answer 28

1. degradation refers to TTP and ADAMS13 enzyme

Question 29

TTP - inherited or acquired?

Answer 29

Either - inherited inactivating mutation in ADAMS13 or acquired with antibodies against ADAMS13

Question 30

TTP treatment

Answer 30

plasmapheresis or fresh frozen plasma if not available; hemodialysis

Question 31

Pathogenesis of HUS

Answer 31

gastroenteritis caused by E.coli strain O157:H7 which produces a toxin that causes platelet activation

Question 32

In both TTP and HUS, (1) are formed in various vascular beds, (2) of red cells thus occurs with organ dysfunction in the occluded areas

Answer 32

1. occlusive hyaline thrombi 2. mechanical hemolysis

Question 33

What are the peripheral blood findings of ITP?

Answer 33

large platelets - indicative of increased turnover

Question 34

What are the bone marrow aspirate biospy (BMAB) findings of ITP?

Answer 34

increased megakaryocytes

Question 35

Platelet transfusions contraindicated except for life threatening bleed

Answer 35

TTP and HUS (non-immunologic destruction of platelets)

Question 36

What toxin causes HUS?

Answer 36

Shiga like toxin of EHEC O157:H7