Platelet Disorders Flashcards
platelets - basics
*disc shaped, 2-4 micrometers, anuclear
*blue/gray with reddish/purple granules
*normal counts 150k-400k
*circulate for 7-9 days
*2/3 in circulating blood, 1/3 in spleen
*precursor = megakaryocyte
thrombopoietin (TPO) & platelet production
*a glycoprotein that binds to its receptor on platelets and megakaryocytes
*produced at a constant rate by the liver
*inverse relationship b/w serum TPO levels and platelet mass
*TPO concentration regulated by the total mass of platelets/megakaryocytes available to bind and degrade the protein
components of a platelet
*open canalicular system
*lysosome
*mitochondria
*alpha granules: fibrinogen, von Willebrand factor, platelet factor 4
*dense granules: ADP, serotonin
events of primary hemostasis
- following blood vessel injury, platelets adhere to the exposed subendothelial connective tissues
- under the influence of shear stress, platelets move along the surface of vessels until the platelet engages sub-endothelial collagen (and/or vWF)
platelet functions
- initial function - formation of mechanical plugs during the normal hemostatic response to vascular injury
- local release of potent paracrine vasoconstrictors to decrease blood flow to the injured area
- catalysis of reactions of the soluble coagulation cascade leading to fibrin clot formation (secondary formation)
- initiation of the tissue repair process
- regulation of local inflammation
thrombocytopenia
*defined as platelet count < 150,000 microliters
*consequences:
-bleeding following surgery or trauma with PLT counts < 50k
-spontaneous hemorrhage with platelet counts < 10k
-transfusion threshold
examples of failure of platelet production causing thrombocytopenia
- selective megakaryocyte depression
-rare congenital defects
-drugs, chemicals, viral infections - part of general bone marrow failure
-cytotoxic drugs (chemo)
-radiation
-marrow infiltration
-HIV infection
examples of consumptive thrombocytopenias
- immune
-autoimmune/idiopathic (ITP)
-infections: HIV, malaria
-drug-induced
-HIT
-post-transfusional purpura - disseminated intravascular coagulation (DIC)
- thrombotic thrombocytopenia purpura (TTP)
immune thrombocytopenic purpura (ITP) - acute
*abrupt onset of bleeding, petechiae, mucosal bleeding in a previously healthy person
*may follow an infection, usually a nonspecific URI or GI virus
*majority recover without treatment
*giant platelets appear
treatment of immune thrombocytopenic purpura (ITP)
- target the immune system:
-steroids
-splenectomy
-immune globulin
-rituximab
-splenic tyrosine kinase inhibitors - increase platelet production
-thrombopoietin receptor agonists stimulate megakaryocytes
heparin induced thrombocytopenia (HIT) - overview
*despite thrombocytopenia, one of the most thrombotic conditions -> platelet ACTIVATING
*IgG Abs directed agsint heparin-platelet factor 4 complex
*suspect if platelet count falls to < 100,000 5-15 days after heparin therapy started
**venous, arterial, and microvascular thrombosis threatens life and limb
*risks: any patient on heparin
thrombotic thrombocytopenic purpura (TTP) - clinical presentation
*devastating disorder; fatal if untreated
*clinical “pentad”:
1. fever
2. anemia
3. thrombocytopenia
4. renal dysfunction
5. neurologic deficits
*blood film: schistocytes + few platelets
thrombotic thrombocytopenic purpura (TTP) - pathophysiology
*the absence or impairment of ADAMTS13 (vWF cleaving enzyme) allows for the persistence of the ultralarge “sticky” forms of vWF, which trap platelets and cause thrombi in vessels
*leading to end-organ damage and the appearance of the pentad of clinical features
contraindications to platelet transfusion
TTP (thrombotic thrombocytopenic purpura) and HIT (heparin induced thrombocytopenia)
pseudothrombocytopenia
*due to in vitro agglutination of platelets (platelets low in test tube because the platelets clump in there, not in body)
