CP1

Question 1

What change occurs in platelets upon stimulation?

Answer 1

Change in shape from discoid to spherical, extend pseudopods, undergo internal contraction, resulting in centralization of granules and release of contents

Platelets release contents from a-granules, dense granules, and lysosomal granules depending on the stimulus strength.

Question 2

What is congenital thrombocytopenia?

Answer 2

A condition that may present with isolated thrombocytopenia or in conjunction with characteristic syndromes

It has increasing frequency and several distinct genetic abnormalities.

Question 3

What is the risk associated with misdiagnosis in congenital thrombocytopenia?

Answer 3

Risk for misdiagnosis as immune thrombocytopenia and unnecessary therapy

This includes treatments like splenectomy.

Question 4

Which mutations have prognostic implications in congenital thrombocytopenia?

Answer 4

RUNX1 and ANKRD26 mutations; MYH9 mutations

RUNX1 and ANKRD26 are associated with myeloid malignancies, while MYH9 mutations are linked to worsening renal function or hearing loss.

Question 5

What are MYH9-related macrothrombocytopenias?

Answer 5

A group of disorders resulting from mutations in MYH9, characterized by increased platelet size and cytoplasmic inclusions in leukocytes

Includes May-Hegglin anomaly, Fechtner syndrome, Epstein syndrome, and Sebastian syndrome.

Question 6

What is familial platelet disorder with predisposition to acute myeloid leukemia?

Answer 6

A condition secondary to mutations in the RUNX1 gene, characterized by normal platelet size but abnormal function.

Question 7

What characterizes platelet-type von Willebrand disease?

Answer 7

Thrombocytopenia, gain-of-function mutations in GPIBA, and enhanced responsiveness to ristocetin on platelet aggregation.

Question 8

What are the features of DiGeorge syndrome?

Answer 8

Cardiac abnormalities, parathyroid and thymus insufficiencies, cognitive impairment, and facial dysmorphology

This syndrome is associated with deletions within 22q11.

Question 9

What are the manifestations of Paris-Trousseau/Jacobsen syndrome?

Answer 9

Psychomotor retardation and facial and cardiac abnormalities

Arises due to deletion within 11q 23-24.

Question 10

What is classical Bernard-Soulier syndrome?

Answer 10

A rare autosomal recessive disorder characterized by macrothrombocytopenia due to biallelic mutations in the GPIb-IX-V complex.

Question 11

What defines congenital amegakaryocytic thrombocytopenia (CAMT)?

Answer 11

Mutations in the thrombopoietin receptor MPL, characterized by severe thrombocytopenia and absence of megakaryocytes in the bone marrow.

Question 12

What is thrombocytopenia with absent radii (TAR) syndrome associated with?

Answer 12

Skeletal abnormalities.

Question 13

What is Wiskott-Aldrich syndrome (WAS)?

Answer 13

A condition characterized by mutations in the WAS gene, leading to small platelets and thrombocytopenia.

Question 14

What is the primary diagnosis of immune thrombocytopenia (ITP)?

Answer 14

A diagnosis of exclusion made in the absence of other causes or disorders associated with thrombocytopenia.

Question 15

What platelet count threshold is recommended for diagnosing ITP?

Answer 15

<100,000 platelets/µL

This threshold seeks to avoid overdiagnosis in apparently healthy individuals.

Question 16

What is the significance of antecedent infectious diseases in pediatric ITP patients?

Answer 16

Approximately 60% of pediatric ITP patients have a history of antecedent infectious diseases.

Question 17

What are the common drugs implicated in drug-induced immune thrombocytopenia (DITP)?

Answer 17

Quinine, quinidine, trimethoprim-sulfamethoxazole, vancomycin, and piperacillin/tazobactam.

Question 18

What clinical features are associated with DITP?

Answer 18

Platelet count <20,000/µL and bleeding symptoms that typically begin 5 to 10 days after starting the drug.

Question 19

What is the distinction between primary and reactive thrombocytosis?

Answer 19

Primary is related to autonomous clonal bone marrow disorders, while reactive is secondary to conditions like infections or chronic inflammation.

Question 20

What cytogenetic abnormalities are associated with primary thrombocytosis?

Answer 20

JA K2V 617F and calreticulin mutations.

Question 21

What defines the bleeding time in Bernard-Soulier syndrome?

Answer 21

Bleeding time is markedly prolonged with moderately decreased platelet counts.
Platelets increased in size

decreased/absent response to Ristocetin

Question 22

What is the hallmark diagnostic feature of Glanzmann thrombasthenia?

Answer 22

• Absence or marked impaired platelet aggregation in response to activation with all physiologic agonists,
• prolonged bleeding time,
• severe mucocutaneous bleeding manifestations.

Pry - Defect in GPIIb-GPIIIa complex.
Lack of platelet-platelet clumping
DX- absence/marked decreased of platelet aggregation in response to virtually all platelet agonists except ristocetin.

Question 23

DISORDERS OF PLATELET AGGREGATION

What distinguishes gray platelet syndrome?

Answer 23

Gray appearance of platelets with paucity of granules in peripheral blood smears.

Isolated def. of a-granule contents is heterogenous disorder

Question 24

What is the effect of aggregation responses to ADP and epinephrine in most patients?

Answer 24

Normal aggregation responses

Aggregation responses to thrombin, collagen, and ADP have been impaired.

Question 25

What is vWF and how is it synthesized in patients with certain disorders?

Answer 25

vWF is synthesized but secreted into the extracellular space instead of normal a-granule packaging ## Footnote This occurs due to failure of a-granule maturation during megakaryocyte differentiation.

Question 26

What is Quebec Platelet Disorder (QPD)?

Answer 26

* An autosomal dominant disorder associated with * delayed mucocutaneous bleeding, * abnormal proteolysis of a-granule proteins, * defective aggregation selectively with epinephrine ## Footnote Other features include normal to reduced platelet counts and deficiency of the factor V-binding protein multimer.

Question 27

Which proteins are degraded in patients with QPD?

Answer 27

Platelet factor V and other a-granule proteins ## Footnote This includes fibrinogen, vWF, thrombospondin, osteonectin, fibronectin, and P-selectin.

Question 28

How do patients with QPD respond to platelet transfusions?

Answer 28

Mucocutaneous bleeding following injury is unresponsive to platelet transfusions but responsive to fibrinolytic inhibitors.

Question 29

What defects are associated with platelet-agonist interactions?

Answer 29

Defects in platelet-agonist interaction include epinephrine, collagen, ADP, TxA2, and activating factor ## Footnote Some patients have an Arg60-to-Leu mutation of the human TxA2 receptor.

Question 30

What is the role of G-proteins in platelet signal transduction?

Answer 30

G-proteins link surface receptors and intracellular effector enzymes; defects can impair signal transduction.

Question 31

What are the laboratory findings in patients with platelet signal transduction defects?

Answer 31

Mild bleeding diathesis, abnormal aggregation, and dense granule secretion in response to weaker agonists i.e; epinephrine, ADP, PAF ## Footnote Stronger agonists such as arachidonate and high concentrations of collagen may elicit normal responses.

Question 32

What is the major platelet response to activation?

Answer 32

Impaired Liberation of arachidonic acid from membrane phospholipids, followed by conversion to TxA2.

Question 33

What condition is characterized by thrombocytopenia with small platelets, immunodeficiency, and eczema? ## Footnote It affects T lymphocytes and platelets

Answer 33

Wiskott-Aldrich Syndrome (WAS) ## Footnote It arises from mutations in the gene coding for the WAS protein.

Question 34

What characterizes LAD-III? (Kindlin-3 Deficiency-Leukocyte Adhension Deficiency)

Answer 34

Hemorrhagic diathesis, predisposition to infections & imflammation without pus formation, and poor wound healing ## Footnote Kindlin-3 binds to the cytoplasmic domain of the integrin β3 subunit of αIIbβ3.

Question 35

What is Scott syndrome? ## Footnote Disorder of Platelet Procoagulant Activites

Answer 35

A disorder where platelet contribution to blood coagulation is impaired. Mutation - TMEM16F ## Footnote Aggregation and secretion responses are normal. Bleeding time and platelet aggregation are normal, PTT- Normal

Question 36

What role does von Willebrand factor (vWF) play in hemostasis?

Answer 36

vWF mediates platelet adhesion to exposed collagen at sites of vascular injury and serves as a carrier protein for factor VIII.

Question 37

What is the function of ADAMTS-13?

Answer 37

It cleaves unusually large von Willebrand factor (vWF) multimers, preventing excessive platelet aggregation under high shear stress conditions.

Question 38

What are the characteristics of thrombotic thrombocytopenic purpura (TTP)?

Answer 38

It may be congenital or acquired; characterized by thrombocytopenia and microangiopathic hemolytic anemia ## Footnote Neurologic abnormalities or other organ injury signs are typically seen.

Question 39

What is the effect of aspirin on platelet function?

Answer 39

It inhibits platelet aggregation and secretion upon stimulation with ADP, epinephrine, and low concentrations of collagen ## Footnote Aspirin irreversibly acetylates and inactivates platelet cyclooxygenase.

Question 40

What is the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on platelets compared to aspirin?

Answer 40

NSAIDs generally have a short-lived and reversible inhibition of cyclooxygenase compared to aspirin.

Question 41

What is the clinical history suggesting in patients with suspected congenital platelet disorders?

Answer 41

A bleeding tendency.

Question 42

What are the levels of ADAMTS-13 in relation to TTP in E-coli or Shiga like toxin?

Answer 42

ADAMTS-13 levels are not decreased to the low levels associated with TTP.

Question 43

What type of cells do long vW F strings bind to?

Answer 43

Long vW F strings bind to both endothelial cells and platelets.

Question 44

What may interfere with ADA MTS-13 binding to vW F strings?

Answer 44

A toxin may interfere with ADA MTS-13 binding to the vW F strings.

Question 45

What is a common clinical history indicator for congenital platelet disorders?

Answer 45

A clinical history suggesting a bleeding tendency.

Question 46

What might a platelet count help determine?

Answer 46

Whether the bleeding tendency is explicable by thrombocytopenia alone.

Question 47

What does a prolonged PFA-100 or bleeding time suggest?

Answer 47

A platelet defect may be present.

Question 48

What can be normal in patients with platelet function defects?

Answer 48

Prolonged FA-100 and Bleeding time can be normal.

Question 49

What is evaluated simultaneously with plasma factor VIII?

Answer 49

vW F (von Willebrand factor).

Question 50

What is more common in patients with mucocutaneous bleeding manifestations?

Answer 50

vW D is more common than congenital platelet defects.

Question 51

What does the ristocetin cofactor assay measure?

Answer 51

vWF functional activity with platelets.

Question 52

What does a decrease in FVIII activity to von Willebrand factor antigen level indicate?

Answer 52

It may be used to predict carrier status of hemophilia A.

Question 53

What are the two types of hereditary fibrinogen abnormalities?

Answer 53

* Type I: Afibrinogenemia or hypofibrinogenemia * Type II: Dysfibrinogenemia or hypodysfibrinogenemia.

Question 54

What can prolonged PT and APTT indicate?

Answer 54

General medical conditions.

Question 55

What are common causes of acquired bleeding disorders?

Answer 55

* Anticoagulation * Disseminated intravascular coagulation (DIC) * Liver disease * Vitamin K deficiency * Massive transfusion * Unique inhibitors to coagulation proteins.

Question 56

What is DIC?

Answer 56

A clinicopathologic condition with activation of coagulation and fibrinolysis systems.

Question 57

What factors are synthesized in the liver?

Answer 57

* Factors II * VII * IX * X * Protein C * Protein S * Protein Z.

Question 58

What is defined as massive transfusion?

Answer 58

Replacement of more than 1.5 blood volume in 24 hours.

Question 59

What is dilutional coagulopathy?

Answer 59

Results from replacement with packed red blood cells and normal saline without clotting factors or platelets.

Question 60

Who are typically seen with inhibitors against FVIII?

Answer 60

* Elderly patients * Patients with B-cell malignancies * Patients with connective tissue disorders - i.e SLE * Postpartum patients.

Question 61

What does the lupus anticoagulant phenomenon influence?

Answer 61

Coagulation protein reactions directed to epitopes of proteins bound to phospholipids.

Question 62

What is the effect of antiphospholipid antibodies in vitro?

Answer 62

They prolong clottings assays like APTT, dRVVT, and KCT and Prothrombin time (less frequently).

Question 63

Are patients with lupus anticoagulant at risk for bleeding?

Answer 63

False; they may be at risk for THROMBOSIS.