Lecture #8: Quantitative and Qualitative Platelet Disorder

Question 1

What sundrome associated with Small platelet that is less than 7 fL MPV

Answer 1

Wiskot-Aldrich Syndrome

Question 2

Encodes the nonmuscle myosin heavy chain IIA, a contractile cytoskeletal protein

mutation result in disorder production of the nonmuscle myosin heavy chain IIa

Answer 2

MYH9-RELATED MACROTHROMBOCYTOPENIA

Question 3

Most commonly implicated drugs

Answer 3

Quinine
quinidine
trimethoprim-sulfamethoxazole
vancomycin, and pipericillin/tazobactam

Question 4

GPIIb-IIIa antagonist drugs
- Acute severe thrombocytopenia may occur, even following
the first exposure to the drug

Answer 4

“Fibans” (eptifibatide and tirofiban

Question 5

Chimeric human-mouse Fab fragment specific for GP IIIa
- Preexisting antibodies causing the DITP target structural
elements in the abciximab molecule that are of murine origin

Answer 5

Abciximab

Question 6

Cause DITP via drug-dependent antibodies targeting epitopes

on platelet:

Answer 6

Quinine & Sulfonamides

Question 7

Induce autoantibodies that have specificity for platelet GP

Answer 7

Heparins and protamine

Question 8

results from gain-of-function mutations in either

thrombopoietin or its receptor (MPL)

Answer 8

Congenital Thrombocytosis

Question 9

Rare autosomal recessive platelet function disorder
resulting from an abnormality in the platelet GP Ib-IX-V
complex ,

Answer 9

Bernard-Soulier syndrome (BSS)

Question 10

Rare autosomal recessive disorder resulting from a
quantitative or qualitative defect in the GPIIb-IIIa complex →
Impaired fibrinogen binding to platelets on activation and
aggregation
- More severe mucocutaneous bleeding manifestations than
most platelet function disorders

Answer 10

Glanzmann Thrombasthenia

Question 11

• Autosomal dominant disorder
• Associated with delayed mucocutaneous bleeding and
  abnormal proteolysis of α-granule proteins

Answer 11

Quebec Platelet Syndrome

Question 12

An X-linked inherited disorder affecting T lymphocytes

and platelets

Answer 12

Wiskott-Aldrich Syndrome

Question 13

Mutations in kindlin-3, which is encoded by the
FERMTS3 gene, is associated with markedly abnormal
aggregation responses to multiple agonists resembling
Glanzmann Thrombasthenia (GT) and features of mild
leukocyte adhesion–deficiency (LAD) III disorder

Answer 13

Kindlin-3 Deficiency–Leukocyte Adhesion Deficiency

Question 14

Platelet contribution to blood coagulation is impaired, but

aggregation and secretion responses are normal

Answer 14

Scott Syndrome

Question 15

• Carrier protein for plasma FVIII
• Ligand that binds to GP Ib receptor on platelets to
  initiate platelet adhesion

Answer 15

von Willebrand Factor

Question 16

Primary measure of vWF functional activity for many

years

Answer 16

“Ristocetin cofactor” assay

Question 17

enhances the binding of vWF to platelet

GPIbα

Answer 17

Ristocetin

Question 18

vWF collagen binding activity

Answer 18

wells are coated with type 3 or a mixture of types 1 and
3 collagen, patient plasma incubated in the wells, and
bound vWF subsequently quantitated by means of
conjugated anti-vWF antibody

Question 19

Autosomal dominant inheritance
- vWF molecules are present in decreased amount in plasma,
but are qualitatively normal
Most common vWD subtype (75%)

Answer 19

Type 1 vWD: Partial Quantitative Abnormality

Question 20

Autosomal recessive inheritance

- Severe , if not in fact total, absence of vWF gene product

Answer 20

Type 3 vWD: Severe Quantitative Abnormality

Question 21

Lack of higher molecular weight multimers in plasma with
corresponding loss of vWF functionality
- Arise due to vWF mutations that prevent proper
multimerization or to mutations that increase the
susceptibility of fully formed vWF to proteolysis by ADAMTS13
or other enzymes.

Answer 21

Type 2A: Qualitative Abnormality

Question 22

have a decrease-of-function phenotype resembling type 2A,
without lack of higher molecular weight multimers
- Had missense mutations that led to loss of interaction with
the platelet GPIb-IX-V complex

Answer 22

Type 2M: Qualitative Abnormality

Question 23

Clinicopathologic condition in which activation of the
coagulation and fibrinolysis systems results in the
simultaneous formation of thrombin and plasmin with
consumption of coagulation factors and inhibitors of the
system, resulting in the clinical laboratory phenotype of
prolonged PT, APTT, and thrombocytopenia

Answer 23

Disseminated Intravascular Coagulation (DIC

Question 24

• Used to recognize DIC
• May variably represent plasmin-cleaved fibrinogen, soluble
  fibrin, or insoluble fibrin

Answer 24

Fibrin Degradation (Split) Products (FDPs)

Question 25

Responsible for γ-carboxylation reaction of a number of glutamic acid residues within coagulation factors II, VII, IX, and X and proteins C, S, and Z

Answer 25

Vitamin K

Question 26

Plt count drop that begins within 5 to 10 days of starting heparin therapy Associated with substantial morbidity and mortality, necessitating early diagnosis and initiation of appropriate therapeutic measures

Answer 26

Heparin-Induced Thrombocytopenia

Question 27

Detect antibodies that binds to platelet factor IV/Heparin | complexes

Answer 27

Immunoassays (ELISA)

Question 28

Gold standard in US: Washed platelets that have taken up exogenous 14C-labeled serotonin are challenged with patient plasma in the presence of different heparin concentrations, and the amount of released serotonin is measured as the endpoint

Answer 28

Serotonin Release Assay

Question 29

Arise due to deletions within chromosome 22q11

Answer 29

Velocardiofacial syndrome and DiGeorge syndrome

Question 30

Due to deletion of a portion of chromosome 11,11q23-24 Platelets are increased in size and have giant and defective α-granules

Answer 30

Paris-Trousseau/Jacobsen Syndrome

Question 31

Gene that Helps in the regulation of the development of | blood cells

Answer 31

FLI-1 gene/ friend leukemia integration | 1ne

Question 32

Associated with mutations in GPIbα and considered a | heterozygous form of Bernard-Soulier syndrome

Answer 32

Mediterranean Macrothrombocytopenia, Bolzano Variant

Question 33

Resulting from a point mutation in a leucine tandem | repeat of GPIbα

Answer 33

Autosomal Dominant Bernard-Soulier Syndrome

Question 34

Lead to constitutive activation of the GPIIb-IIIa integrin | complex

Answer 34

Mutations in GPIIb or GPIIIa

Question 35

Associated with mutations in the thrombopoietin receptor MPL - Characterized by severe thrombocytopenia and absence of megakaryocytes in the bone marrow

Answer 35

Congenital Amegakaryocytic Thrombocytopenia (CAMT)

Question 36

Linked to mutations in the NBEAL2 gene = encodes a | BEACH protein involved in vesicular trafficking

Answer 36

Gray platelet syndrome

Question 37

Thrombocytopenia is associated with skeletal | abnormalities

Answer 37

Absent Radii (TAR) Syndrome

Question 38

- Mutations in the WAS gene - Characteristically have small platelets - Thrombocytopenia may occur in the absence of other immunologic features of the syndrome

Answer 38

Wiskott-Aldrich syndrome (WAS) and the Related X-linked | thrombocytopenia

Question 39

Regulates the expression of genes that mediate | the development of RBCs and plts

Answer 39

GATA-1 Aka Erythroid transcription factor

Question 40

Heterogeneous group of disorders characterized by autoimmune-mediated platelet destruction and impaired platelet production

Answer 40

Immune Thrombocytopenias

Question 41

Autoimmune disorder characterized by isolated thrombocytopenia (peripheral platelet count <100 × 10 9 /L) in the absence of other causes and disorders that may be associated with thrombocytopenia

Answer 41

Primary ITP

Question 42

Consists of all forms of immune-mediated thrombocytopenia except primary ITP - Due to other diseases

Answer 42

Secondary ITP

Question 43

Main clinical problem of primary ITP

Answer 43

an increased risk for bleeding

Question 44

Closest to what could be considered a reference methodology - Through incubation of freshly obtained donor platelets with patient serum or with eluates from patient platelets, Challenging; labor intensive and requires the availability of previously characterized platelet donors

Answer 44

Monoclonal Antibody Immobilization of Platelet Antigen (MAIPA) Technique

Question 45

Caused by platelet destruction through immunologic | mechanisms

Answer 45

Drug-Induced Immune Thrombocytopenia (DITP)

Question 46

Characterized by thrombocytopenia, gain-of-function mutations in GPIBA, and enhanced responsiveness to ristocetin on platelet aggregation

Answer 46

Platelet-Type vWD

Question 47

Regulates the differentiation of hematopoietic | stem cells into mature blood cells

Answer 47

RUNX1 = runt-related transcription factor 1

Question 48

Thrombocytopenia is secondary to mutations in the | RUNX1/ CBFA2/AML1 gene

Answer 48

Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML)

Question 49

What condition that mutation resukt in disordered production of the nonmuscle myosin heavy chain IIa

Answer 49

MYOSIN HEAVY CHAIN 9-Related Macrothrombocytopenias/ MYH9-related Macrothrombocytopenia

Question 50

T/F. Congenital Thrombocytopenias is associated with mutations in genes

Answer 50

Trueness

Question 51

What syndromes is classified as small platelets

Answer 51

Wiskot-Aldrich Syndrome | X linked Thrombocytopenia

Question 52

What gene differentiate hematopoeitic stem cells imto maturation blood cells

Answer 52

RUNX1

Question 53

What disease that is present in approximately 60% of pediatric ITP patients? What are those infection

Answer 53

Antecedent Infectious disease HIV and HCV infection og H. Pylori Infection

Question 54

T/F. EDTA is used during blood collection in DITP

Answer 54

False. EDTA should be avoided!!!!

Question 55

What substance that enhances the binding of vWF to Platelet GPIB alpha

Answer 55

Ristocetin

Question 56

T/F. It is the low molecular weight multimers thar are most active in binding to platelets

Answer 56

False. higher molecular weight of multimers dapat hehe