Hemostais: Approach to patient Flashcards
Discuss events occurring during hemostasis, comparing primary and secondary hemostasis
Primary: Adhesion, activation, and aggregation of platelets to form a platelet plug
Secondary: The platelet plug is stabilized by formation of a fibrin network generated through the coagulation cascade
3 functions of proteins:
- adhesion to the vascular subendothelium at sites of injury to begin the hemostatic process
- activation of intracellular signaling pathways leading to cytoskeletal changes and release of intracellular granules to enhance platelet plug formation
- aggregation to form the platelet plug
Explain why platelet adhesion to blood vessels does not occur under normal circumstances.
This will not happen under normal circumstances because with vessel damage, subendothelial components which are not usually exposed are exposed.
NORMALLY: endothelial cells of intact vessel prevent blood coagulation by secretion of a heparin-like molecule and through expression of thrombomodulin, which when bound to thrombin activtes protein C and S. Intact endothelial cells prevent platelet aggregation by the secretion of nitric oxide and prostacyclin, inhibitors of platelet activation
3 mechanisms that could lead to thrombocytopenia
- decreased platelet production
- increased platelet destruction
- consumption/sequestration of platelets in the spleen
Decreased platelet production can be caused by:
- primary bone marrow disorders, myelodysplasia, leukemia
- invasion of the BM by metastatic cancer, myeofibrosis, TB
- Toxins
- nutritional deficiencies
Increased platelet destruction can be caused by:
most common = immune thrombocytopenic purpura (anti-platelet ABs lead to their removal by macrophages)
2 types of ITP and tx
- Acute = more common in children and presents with nosebleeds or viral infection, usually resolves within 2 to 6 weeks sin tratamiento or with steroids
- Chronic = more common in adults with autoimmune disorders, most requiring treatment
- Treatment methods include corticosteroids, Intravenous immunoglobulin (IVIG), and splenectomy.
Consumption/sequestration of platelets in spleen occurs when
when endothelial damage leads to an abnormally large release of abnormally large vWF from storage sites. The vWF is abnormally large because metalloprotease ADAMTS13, whose normal function is to digest large vWF multimers into small multimers, is absent. These vWF molecules mediate platelet adhesion and aggregation forming diffuse arteriole plugs
tx for TTP
by plasmapheresis to remove the large vWF multimers and replace the ADAMTS13
Identify three methods of treating ITP
Corticosteroids
Intravenous immunoglobulin (IVIG)
Splenectomy
Corticosteroids: mechanism by which it increases the platelet count.
slow the proliferation of the B-cell clone making the auto antibodies. Work within 7-10 days
IVIG: mechanism by which it increases the platelet count.
acts by blocking splenic Fc receptors to prevent their binding to antibody-coated platelets – effect seen 1 to 2 days.
splenectomy: mechanism by which it increases the platelet count.
removes the site where the majority of autoantibody induced platelet removal is occurring. Lasting effects in 60 to 70% of patients
Describe the molecular defect in VWD
-vWD is the most common congenital bleeding disorder. It can be caused by autoantibodies against the von Willebrand Factor (vWF), an inadequate amount of vWf, or mutations in the vWF gene
what is the typical clinical course of WVD
Lack of or alteration in the vWF can lead to an abnormal platelet/endothelial interaction leading to a bleeding disorder. Since vWF is also a carrier for Factor VIII, severe vWD can lead to factor VIII deficiency and a disorder with secondary hemostasis.
