platelet Flashcards
What platelet aggregation pattern is characteristic of dense granule deficiency?
Decreased aggregation to ADP and epinephrine (normal primary wave, no secondary wave)
Blunted response to collagen
Normal response to ristocetin
What are the key laboratory findings in Glanzmann thrombasthenia?
Normal platelet size and count
Abnormal aggregation to ADP, epinephrine, and collagen
Normal response to ristocetin
What are the key laboratory findings in Bernard-Soulier syndrome?
Macrothrombocytes
Variable thrombocytopenia
No platelet response to ristocetin
Normal aggregation to ADP, epinephrine, and collagen
What is the cause of platelet-type or pseudo–von Willebrand disease?
Mutation in glycoprotein 1b receptor leading to increased binding with von Willebrand factor.
How is dense granule deficiency diagnosed?
Electron microscopy to count dense granules (normal platelets have 3-8 dense granules).
What is gray platelet disorder, its inheritance pattern, clinical progression, and key laboratory findings?
A platelet disorder characterized by deficiency or absence of α-granules, leading to gray appearance on Wright-stained smears.
Clinical Features: Macrothrombocytopenia, mild to moderate mucocutaneous bleeding, progressing to splenomegaly and myelofibrosis in adulthood.
Lab Findings:
Nonspecific platelet aggregation abnormalities, macrothrombocytes.
Diagnosis: Confirmed by electron microscopy (absence of α-granules) or flow cytometry analysis of α-granule release.
What is the deficiency associated with alpha granules?
Gray platelet syndrome
What is the deficiency associated with dense granules?
Hermansky-Pudlak syndrome, Chediak-Higashi syndrome (CHS)
Alpha granules content
ITPPTPVF
I – IGF1
T – TGFβ
P – PDGF
P – PF4
T – Thrombospondin
P – P-selectin
F – Fibronectin
V – Factor V
V – VWF
Why in Glazmann Aggregation to ristocetin is preserved ?
because this tests the interaction of factor glycoprotein complex Ib-IX with von Willebrand
Increased aggregation to low-dose ristocetin occurs **
in platelet-type von Willebrand disease (vWD) and type 2B vWD.
Both conditions result in increased binding of platelets to von Willebrand factor
platelet-type vWD the defect is glycoprotein Ib on the platelets, whereas in type 2B vWD the mutation is in the von Willebrand factor molecule.
TTP
TTP results when the metalloprotease ADAMTS13, responsible for cleaving ultralarge multimers of von Willebrand factor (vWF), is either absent (congenital) or inhibited by antibodies (acquired). Without this protease, platelets bind to large vWF multimers and form microthrombi, resulting in thrombocytopenia and microangiopathic hemolytic anemia.
TTP is a medical emergency, so prompt recognition and initiation of plasmapheresis are essential. Guidelines also recommend the addition of corticosteroids to plasmapheresis and suggest that Rituximab may also be helpful. The guidelines finally suggest that
caplacizumab can be adding to these therapies. This drug works by blocking the A1 domain of von Willebrand factor, thereby blocking it from interacting with glycoprotein 1b on the platelets. This reducing the microthrombi formation.
This mutation results in impaired production of an RNA-binding protein. The resulting effect on platelets is the formation of large alpha granules that can be appreciated on electron microscopy.
Ch22q11, as well as Jacobson/Paris-Trousseau syndromes, involve mutations in Ch22q11.
Thrombocytosis seen with ***** is thought to be related to the production of thrombopoietin in the liver. The diagnosis can be confirmed with an abdominal ultrasound and alpha-fetoprotein levels.
hepatoblastoma
Hermansky-Pudlak syndrome,
an autosomal recessive disorder, causes a bleeding diathesis due to a lack of dense granules in the platelets, which is demonstrated on electron microscopy.
The disease is associated with oculocutaneous albinism, pulmonary fibrosis, strabismus, and nystagmus.
Dense granules contain small molecules such as ATP, ADP, serotonin, and calcium. Platelet aggregation studies will therefore show absent second-wave aggregation in response to ADP and epinephrine.
Drug-induced thrombocytopenia can occur several different ways.
Penicillin, the drug serves as a hapten. The drug attaches to the platelet surface, and the antibody then attaches to the drug/platelet complex through the drug.
In heparin-induced thrombocytopenia, an immune complex is formed through drug-plasma protein interaction. Antibodies to this immune complex then bind to the platelet surface via exposed Fc receptors. The classic drug-induced thrombocytopenia seen with quinine occurs through the binding of the drug directly to a platelet domain on the surface of the platelet. This causes a confirmation change that exposes an epitope to which the antibody binds.
Bone marrow suppression can be seen with some drugs such as valproic acid, and thrombocytopenia may not be as severe.
GPIIa/IIIb inhibitors used in cardiac patients have their mechanism of action by direct binding to glycoproteins on the platelet surface. Some patients develop acute, severe thrombocytopenia within hours of the first drug exposure.
Inherited causes of HUS
Complement-mediated HUS
o C3, CFB, CFH, CFI, CD46
* Inborn error of Cobalamin C metabolism
* Diacylglycerol kinase epsilon mutations
