Haematology/ Abnormal Platelet Counts and Abnormal Bleeding

Question 1

What is the term for abnormally increased platelets?

Answer 1

Thrombocytosis or thrombocythemia

Question 2

What are the two main types of thrombocytosis?

Answer 2

1. Essential thrombocytosis (and other myeloproliferative disorders)
2. Secondary thrombocytosis causes:

• iron deficiency anemia
• hemolytic anemia
• surgery
• asplenia
• “rebound” thrombocytosis following period of thrombocytopenia
• acute or chronic infection or inflammation
• cancer
• drug reactions

Question 3

What are the major complications associated with essential thrombocytosis?

Answer 3

Numerous and dysfunctional platelets cause bleeding and thrombotic events.

Question 4

Why do complications of bleeding and thrombosis of ET not exist in secondary thrombocytosis?

Answer 4

Unless the cause of thrombocytosis (eg, cancer) in and of itself places the patient at risk for either bleeding or thrombotic events, the overabundance of platelets do not cause these complications because the platelets still function normally.

Question 5

What is the term for abnormally decreased platelets?

Answer 5

Thrombocytopenia

Question 6

What are the symptoms of thrombocytopenia?

Answer 6

Easy bleeding, which is most often noted at mucosal surfaces (nose bleeds, bleeding gums) and the skin (petechiae, purpura).

Life-threatening hemorrhage may occur in severe cases.

Question 7

What is the most common cause of thrombocytopenia in children?

Answer 7

Idiopathic (immune) thrombocytopenic purpura (ITP)

Question 8

In ITP, what is the cause of platelet destruction?

Answer 8

Autoantibodies coat platelets and accelerate their clearance by macrophages that are usually found in the spleen and liver.

Question 9

In ITP, is platelet destruction the only cause of thrombocytopenia?

Answer 9

No. There is also a decrease in platelet production.

Question 10

What is the medical treatment of ITP?

Answer 10

Watchful waiting (some mild causes resolve spontaneously), or steroids and intravenous gamma globulin (IVIG)

Question 11

What is the surgical treatment of ITP?

Answer 11

Splenectomy (the spleen produces autoantibodies and also removes platelets from circulation)

Question 12

What two diseases are characterized by renal failure, thrombocytopenia, nonimmune (Coombs negative) hemolytic anemia, largely caused by blood clots within the capillaries and arterioles of many organs?

Answer 12

1. Thrombotic thrombocytopenic purpura
2. Hemolytic uremic syndrome

Question 13

What are the mechanisms by which alcoholism can lead to thrombocytopenia?

Answer 13

1. Liver disease → splenomegaly → platelet sequestration
2. B 12 and folate deficiency → decreased platelet production
3. Direct toxic effects of alcohol on platelets and bone marrow

Question 14

What are the mechanisms by which cancer can lead to thrombocytopenia?(3)

Answer 14

1. Primary or metastatic bone marrow lesions → decreased platelet production
2. Cancer treatment (chemotherapy, radiation) → destruction of bone marrow and blood stem cells
3. Complications of cancer such as disseminated intravascular coagulation

Question 15

What are the mechanisms by which liver disease can lead to thrombocytopenia?

Answer 15

1. Portal hypertension → splenomegaly → platelet sequestration
2. Decreased production of thrombopoietin by liver cells → decreased production and differentiation of megakaryocytes

Question 16

By what mechanism do nonsteroidal anti-inflammatory medications, such as aspirin and ibuprofen, reduce inflammation and fever but also increase the risk of bleeding?

Answer 16

• Nonselective inhibition of cyclooxygenases (COX1 and COX2) blocks the pathways which produce prostaglandins and thromboxane.
• Prostaglandins mediate physiologic effects, such as inflammation and fever. Thromboxane increases platelet aggregation.

Question 17

What is disseminated intravascular coagulation (DIC)?

Answer 17

• A pathologic activation of the clotting cascade leads to formation of small clots throughout the vessels.
• Clots cause end-organ ischemia or infarction.
• Clots consume clotting proteins and platelets which causes abnormal bleeding.

Question 18

What are the common lab findings of DIC?

Answer 18

• Decreased platelets (consumption)
• increased PT and aPTT
• positive D-dimers
• decreased fibrinogen

Question 19

What are the most common causes of DIC?

Answer 19

• sepsis
• malignancy
• trauma/surgery
• obstetrical complications (eg, preeclampsia)

Question 20

What is the most common bleeding disorder in the United States?

Answer 20

Von Willebrand disease

Question 21

What is the Mendelian inheritance pattern of hemophilia?

Answer 21

X-linked recessive (thus, females are rarely affected)

Question 22

What clotting factor is lacking in hemophilia A?

Answer 22

Factor VIII

Question 23

What clotting factor is lacking in hemophilia B?

Answer 23

Factor IX

Question 24

What are the major complications of hemophilia?

Answer 24

• Severe internal bleeding (intracranial hemorrhage, hemarthrosis with significant joint damage)
• adverse reaction to clotting factor treatment
• infection transmitted via blood transfusion (much less common nowadays)