Platelet Disorders

Question 1

How do you differentiate a thrombocytopenia of production vs destruction?

Answer 1

In destruction, you will see few platelets overall and the ones you do see will be large, as young platelets tend to be much larger.

Question 2

Platelets are recycled in. . .

Answer 2

. . . the spleen

Question 3

___ is generally associated with severe thrombocytopenia and may be a harbinger of complications such as gastrointestinal bleeding or even brain hemorrhage.

Answer 3

Mucosal purpura is generally associated with severe thrombocytopenia and may be a harbinger of complications such as gastrointestinal bleeding or even brain hemorrhage.

Question 4

Platelet disorders table

Answer 4

Question 5

Primary hemostasis defects cause ___.

Secondary hemostasis defects cause ___.

Answer 5

Primary hemostasis defects cause superficial bleeding, petechiae, ecchymoses.

Secondary hemostasis defects cause deep bleeding, hematoma, hemarthralgia.

Question 6

Decreased production of platelets differential

Answer 6

• Aplasia
• BM invasion
• Drugs/toxins
• TPO deficiency

Question 7

Increased destuction of platelets differential

Answer 7

• Immune thrombocytopenia
• TTP
• HUS
• DIC
• Spleen hyperplasia (sequestration)
• Thrombosis (sequestration)

Question 8

Most individuals with immune thrombocytopenia present to a hospital with ___.

Answer 8

Most individuals with immune thrombocytopenia present to a hospital with immune thrombocytopenic purpura.

Question 9

In the majority of ITP patients, symptoms. . .

Answer 9

. . . resolve within 6 months, even without therapy

Question 10

Presentation of ITP in children and young adulst

Answer 10

Typically present in younger individuals that are otherwise healthy with the sudden appearance of petechiae or ecchymoses a few days or weeks after an infectious illness, which is usually viral in nature

Question 11

Why is it tough to detect antibodies on platelets?

Answer 11

Platelets have Fc receptors! They are going to have tons of antibodies on them and most won’t be pathologic

Question 12

Presentation of ITP in adults

Answer 12

Adults with ITP have a strikingly different clinical presentation and course. In these patients, the onset is insidious and seldom accompanied by a viral prodrome. The illness is chronic and, when severe, requires meticulous and often complex management. In both children and adults, if ITP is the primary diagnosis, patients normally have no symptoms or physical findings except for purpura.

No lymphadenopathy, often menorrhagia in women, rarely cerebral hemorrhage.

Question 13

Most common ITP antigen

Answer 13

GPIIb/IIIa

Question 14

How might your treatment recommendation for ITP differ for a 26 yo professional hockey player vs. a 14 yo whose main hobbies were photography and reading vs. a 45 yo patient who was HIV positive?

Answer 14

26 yo: Splenectomy or corticosteroids

14 yo: Observation

45 yo: TPO mimetic or IVIG

Question 15

Bone marrow biopsy of ITP

Answer 15

Increased megakaryocytes

Question 16

Unlike autoimmune hemoltyic anemia, ITP is not associated with ___.

Answer 16

Unlike autoimmune hemoltyic anemia, ITP is not associated with fever and cytokine shock.

Question 17

Answer 17

Marrow biopsy of ITP

Increased megakaryocytes

Question 18

The sudden development of purpura in an asymptomatic patient in whom the hemoglobin level, white blood cell count, and differential count are all normal is very likely to be __.

Answer 18

The sudden development of purpura in an asymptomatic patient in whom the hemoglobin level, white blood cell count, and differential count are all normal is very likely to be ITP.

Question 19

Wet bleeding in ITP indicates ___ treatment.

Answer 19

Wet bleeding in ITP indicates corticosteroid treatment.

Question 20

Drug-induced ITP

Answer 20

Either the drug haptenizes platelet antigens, or modifies antibody affinity to recognize platelet antigens

Question 21

Treatments for ITP

Answer 21

• Observation
• Steroids
• Rituximab
• IVIG
• Splenectomy
• TPO-mimetics
• Antifibrinolytics (to prevent mucocutaneous wet bleeding)
• Anti-D (anti-Rh, old treatment, not used so much anymore, complication is possible hemoltyic anemia)

Question 22

Based on this blood smear and a history of being stable but having fever and diffuse purpura, what is the likely diagnosis?

Answer 22

Thrombotic thrombocytopenic purpura

Question 23

Based on this blood smear and a history of being severely unstable, in hypotensive shock, and having diffuse purpura, what is the likely diagnosis?

Answer 23

Disseminated intravascular coagulation

Question 24

Five TTP characteristics

Answer 24

• Thrombocytopenia
• Microangiopathic hemolysis
• Fever
• Renal functional impairment
• Neurologic dysfunction

Question 25

Hemoltyic uremic syndrome

Answer 25

Young children and elderly adults may develop **acute microangiopathic hemolysis** and **thrombocytopenia** accompanied by **oliguria**, **proteinuria,** and **uremia**, often **following a diarrheal illness.** 50% of cases caused by Shiga-toxin or Shiga-like toxins. Most common cause of acute renal failure in young children.

Question 26

TTP vs HUS

Answer 26

In patients with HUS, the anemia and thrombocytopenia are less pronounced than in those with TTP, and neurologic complications are rarely encountered, but the renal impairment is more severe.

Question 27

Atypical HUS

Answer 27

Atypical = nondiarrheal Commonly have an inherited mutation in one of six proteins that are either core components or regulators of the complement cascade: factor H, CD46, factor I, C3, factor B, and thrombomodulin. All of these pathogenic mutations lead to **complement hyperactivity**, which is proposed to produce **endothelial damage and localized thrombus formation**, particularly within the **small vessels of the kidney.** Those with atypical HUS often respond to treatment with **eculizumab**, an antibody directed **against C5** that inhibits the terminal complement cascade.

Question 28

C.O. is an 18 year old female college student with a history of menorrhagia, epistaxis, and easy bruising. She has been in generally excellent health and is currently on no medication except for iron supplements. For the past three years she has experienced nose bleeds, sometimes as often as once per week, without apparent cause. On several occasions, the bleeding was severe enough to require treatment in the E.D. where she received nasal packing. Other family members have a cluster of similar bleeding symptoms. Her platelet count is normal. What is the likely diagnosis?

Answer 28

von Willebrand's disease Interference with primary hemostasis in the absence of thrombocytopenia Likely want to treat with desmopressin and plasma-derived combined vWF-Factor VIII.

Question 29

What is the problem with regular desmopressin?

Answer 29

Eventually the endothelial cells will run out of vWF, so you need to supplement with vWF enriched injections, like plasma-derived vWF-Factor VIII complexes. To avoid this alltogether, you could try antifibrinolytics.

Question 30

Aspirin-poisoned platelets

Answer 30

Question 31

Patients should not take ___ prior to surgery.

Answer 31

Patients should not take **any anticoagulants, including aspirin and other NSAIDs** prior to surgery.

Question 32

While patients with myeloproliferative neoplasms usually have elevated platelet counts, they too often have . . .

Answer 32

While patients with myeloproliferative neoplasms usually have elevated platelet counts, they too often have **prolonged bleeding times.** These patients are highly prone to developing either bleeding or thrombosis. Platelet aggregation studies are frequently abnormal in these patients, but the results have not been helpful in predicting either bleeding or thrombosis.

Question 33

Glanzmann thrombasthenia

Answer 33

Inheritance of a defect in the gene for either **GPIIb or GPIIIa**. As a result, their platelets **lack docking sites for fibrinogen binding.** Even though agonists such as adenosine diphosphate, arachidonic acid, epinephrine, and collagen can activate their platelets, aggregation fails to occur due to the absence of fibrinogen cross-linking. However, **ristocetin still works** in these patients to trigger aggregation, as this is **mediated by vWF**. (Opposite of Bernard-Soulier syndrome)

Question 34

Bernard-Soulier syndrome

Answer 34

Defective GPIb/IX due to mutations in the gene encoding this receptor. Their platelets aggregate normally in response to adenosine diphosphate, arachidonic acid, epinephrine, and collagen but do not aggregate or agglutinate in the presence of ristocetin. (Opposite of Glanzmann thrombasthenia)

Question 35

Storage pool defect

Answer 35

Lack of 'second wave' aggregation due to either lack of or inefficient release of alpha and dense granules. This phenotype may also be induced by aspirin.