Tabares, M.

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PLATELET DISORDERS: SUMMARIZED

Quantitative disorders Qualitative disorders

Thrombocytosis: INHERITED platelet function defects:
 Thrombocythemia  Defects in platelet-vessel wall interaction
 Relative/secondary thrombocytosis o Von Willebrand disease
Thrombocytopenia: o Bernard-Soulier Syndrome
 Decrease production  Defects in platelet-platelet interaction
 Chemo, drug, alcohol o Congenital afibrinogenemia
 Aplastic anemia o Glanzmann thrombasthenia
 TAR  Disorders of platelet secretion and abnormalities of
 Replacement of marrow granules
 Megaloblastic anemia o Storage pool deficiency
 Bernard/soulier o Quebec platelet disorders
 May/hegglin anomaly  Disorders of platelet secretion and signal transduction
 Wiskott/Aldrich syndrome defects
 Increase destruction o Defects in platelet-agonist interaction (receptor
 ITP defects)
 Neonatal alloimmune thrombocytopenia o Receptor defects: thromboxane A2, collagen,
 HDN/HTR adenosine diphosphate (ADP), epinephrine
 HIT o Defects in G-protein activation
 Drug/dependent IgG toplatelet Fc receptors  Gaq deficiency
 Increased sequestration  Gas abnormalities
 Hypersplenism  Gai1 deficiency
 Hypothermia o Defects in phosphatidylinositol metabolism
 Dilutional loss (pregnancy, transfusion) o Phospholipase C-b2 deficiency
 Increase consumption (clotting, MAHA, HUS, DIC, o Defects in calcium mobilization
TTP) o Defects in protein phosphorylation (pleckstrin)
 PKC- deficiency
o Abnormalities in arachidonic acid pathways &
thromboxane A2 synthesis
 Impaired liberation of arachidonic acid
 Cyclooxygenase deficiency
 Thromboxane synthase deficiency
 Defects in cytoskeletal regulation
o Wiskott-Aldrich syndrome
 Disorders of platelet coagulant-protein interaction
(membrane phospholipid defects)
o Scott syndrome

Storage pool Disease

Dense granule deficiency
1. Hermansky-Pudlak Syndrome
2. Wiskott-Aldrich Syndrome
3. Chediak-Higashi
4. TAR (Thrombocytopenia with absent radii)

Acquired platelet function defects:

 Myeloproliferative
 Acute leukemia and myelodysplasia
 Dysproteinemia
 Uremia
 Acquired storage pool diseases
 Anti-platelet antibodies
 Drug-induced
 Tabares, M.A©
Disorders Description Mutated gene
TAR Defect in TPO/TPO-R signaling pathway resulting to hypoplasia of megakaryocyte lineage. RBM8A gene
(Thrombocytopenia Asstd with bilateral radial aplasia.
with absent radii) Hemorrhage in brain and other organs.

May-hegglin Thrombocytopenia and giant platelets. MYH9 gene

anomaly
ITP (Immune Acquired immune mediated disorder.
Thrombocytopenic Low platelet ct <100x10^9/L.
Purpura)
HIT (Heparin- Platelet activation by binding of IgG Fc of drug-dependent IgG to platelet Fc receptors.
induced Catastrophic venous or arterial thrombosis.
thrombocytopenia Non/immune HIT: Type I
; White clot Immune HIT: Type II
syndrome)
Neonatal Infants born to mothers with chronic immune thrombocytopenia.
alloimmune Transplacental passage of maternal IgG platelet autoantibodies.
thrombocytopenia
Post-transfusion Multiparous women.
purpura
TTP (Thrombotic 30 yrs old peak age incidence.
Thrombocytopenic Formation microthrombi in the microvascuature
Purpura) Thrombocytopenia w/ schistocytes.
Inheritance of ADAMTS13 deficiency.
HUS (Hemolytic 6 months and 4 yrs of age.
Uremic Syndrome) E. coli O157:H7
Renal failure.
Small vWF multimers.
Normal ADAMTS13 activity
BSS (Bernard- Platelet lacks GP1b
Soulier Syndrome) Thrombocytopenia with giant platelets
Lab findings
1. Prolonged bleeding time, increased platelet distribution width
2. Normal clot retraction, PT and APTT
3. Normal aggregation test with ADP, collagen and epinephrine
4. Abnormal aggregation with Riscocetin
vWF dse Lack of vWF: carrier protein for factor VIII:C
 Decrease platelet adhesion; mucus bleeding
Lab findings
1. Normal platelet count; prolonged BT
2. Normal PT, variable APTT
3. Normal aggregation test with ADP, collagen and epinephrine
4. Abnormal aggregation with Riscocetin
Glanzmann Population consanguinity is prevalent
Thrombocythemia Platelet lacks GPIIb/IIIa
 Inability of fibrinogen to bind with platelets
 Lack thrombasthenia/actomyosin: clot retraction defect
Lab findings
1. Abnormal aggregation test with ADP, collagen, and epinephrine
2. Normal aggregation with Riscocetin
HPS (Hermansky- Lack of dense body granules
Pudlak Syndrome) Defect in HPS1 and HPS2: formation of a group cell structures called lysosome-related
syndrome
Pigment-producing cells (melanocytes), platelet aggregation & lung cells
Oculocutaneous albinism
Prone to hemorrhage
WAS (Wiskott- lack of any functional WASP WAS gene
Aldrich Syndrome) Relaying signals from the surface of blood cells to the actin cytoskeleton
Movement attachment to other cells and tissues (adhesion) platelet impairs their
development, leading to reduced size and early cell death
Small platelets, thrombocytopenia
 Tabares, M.A©
Decreased alpha and dense granules
Prone to hemorrhage and recurrent infection
Gray platelet Disrupt normal production of alpha granules NBEAL2
syndrome gene
Quebec-platelet Large amounts of fibrinolytic enzyme uPA in platelets, converted to plasmin – responsible
syndrome for degradation
Degradation of proteins stored in platelet alpha granules
Scott Syndrome Defective translocating phosphatidylserine to the platelet membrane inner to outer leaflet
Impaired thrombin formation
Affecting other hematological lineages
Uremia Bleeding caused by platelet dysfunction
Circulating quanidosuccinic acid or hydroxy phenolic acid interference
Altered prostaglandin metabolism
Paraprotein MM, Waldenstrom macroglobulinemia, monoclonal gammopathies, harbor platelet
Disorders dysfunction

Inherited Platelet Disorder:

Autosomal dominant Autosomal recessive X-linked

vWF disorder Bernard-Soulier Wiskott-Aldrich syndrome
Quebec platelet syndrome Glanzmann thrombasthenia Scott Syndrome
May-Hegglin anomaly Gray platelet syndrome
TAR
Hemansky-Pudlak syndrome
Chediak-Hgashi syndrome