Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
30 Cards in this Set
- Front
- Back
|
Platelets basics
|
Disc shaped, 2-4um, anuclear
Blue gray on Wright's stain with reddish-purple granules Normal counts 150-450K Circulate for 7-9 days 2/3rds in blood, 1/3 in spleen |
|
|
Thrombopoietin
|
a glycoprotein that binds to its receptor on platelets and megakaryocytes
produced at a constant rate by the liver inverse relationship between serum TPO levels and platelet mass TPO concentration regulated by the total mass of PLTs/megakaryocytes available to bind and degrade the protein Normal platelet levels allow more eTPO to be bound, leaving less eTPO available to bind to hematopoietic cells -With less eTPO binding to hematopoietic cells, fewer platelets are created by megakaryocytes -Normal platelet counts are maintained In general thrombocytopenia, platelet levels are low -Low platelet levels result in less eTPO bound by TPO-Rs -Serum levels of unbound eTPO are increased -More eTPO is available to bind to progenitor cells and megakaryocytes; platelet production increases -More platelets are released into circulation, allowing platelet levels to return to normal levels |
|
|
Platelet function: primary hemostasis
|
Formation of mechanical plugs during the normal hemostatic response to vascular injury
If absent, spontaneous leakage of blood through small vessels may occur Three components of hemostasis: Blood vessels vasoconstrict Platelets adhere and aggregate Soluble factors have fibrin formation (coag cascade) |
|
|
Platelet vocab: adhesion, activation and secretion, aggregation
|
Adhesion:
Platelets roll and cling to non platelet surfaces Activation and secretion: Soluble factors engage platelet receptors and platelets discharge the contents of their granules Aggregation: Platelets cling to each other |
|
|
Events of primary hemostasis
|
Following blood vessel injury, platelets adhere to the exposed subendothelial connective tissues (collagen).
Under the influence of shear stress, platelets move along the surface of vessels until the platelet engages collagen either directly or via von Willebrand factor. Following adhesion, platelets extrude long pseudopods which enhance interaction between adjacent platelets Platelet activation is then achieved by glycoprotein IIb/IIIa binding fibrinogen to produce platelet aggregation |
|
|
Platelet adhesion, activation and aggregation overview
|
via binding to von Willebrand factor that platelets can bind to collagen. Platelet surface glycoprotein Ib-IX and the glycoprotein IIB/IIIa complex are important in von Willebrand factor binding. Glycoprotein IIb/IIIa is also the fibrinogen receptor that fosters platelet aggregation.
|
|
|
Platelet activation
|
Arachidonic acid pathway to form thromboxane which activates and facilitates aggregation
|
|
|
Mechanism of platelet aggregation
|
Agonist binding to receptors on the platelet surface initiates signal transduction pathways that convert the integrin αIIb3 from its inactive to its active conformation. Then, in the presence of divalent cations such as Ca2+, fibrinogen binds to active αIIb3 on adjacent platelets, cross-linking the platelets into aggregates
|
|
|
Sites of action of anti-platelet drugs
|
Aspirin at cyclo-ocygenase pathway
Dipyridamole at ATP to AMPsite Plavix at ADP sites |
|
|
Secondary hemostasis
|
Platelet plug is stabilized by fibrin (coagulation cascade)
|
|
|
Platelet functions
|
Main function – formation of mechanical plugs during the normal hemostatic response to vascular injury
Local release of vasoconstrictors to decrease blood flow to the injured area Catalysis of reactions of the soluble coagulation cascade leading to fibrin clot formation (ie secondary hemostasis) Initiation of the tissue repair process Regulation of local inflammation |
|
|
Bleeding time
|
Constant pressure (supplied by a sphygmomanometer) of 40 mm Hg. is applied.
5-8 minutes is normal A disposable incision device is used to make an incision 5 mm long x 1 mm deep on the lateral aspect of the volar surface of the forearm. The time to cessation of bleeding is measured. |
|
|
PFA-100 Platelet Function Analysis
|
measures platelet plug formation in a small, whole blood sample Puts platelets under high-shear flow conditions, simulating in vivo conditions.
Platelets first adhere and release and then aggregate to close an aperture in the test cartridge. Closure time reported as normal or abnormal |
|
|
Thrombocytopenia definition and consequences
|
Defined as platelet count <150,000/ul
Consequences -Bleeding following surgery or trauma with PLT counts < 50K -Spontaneous hemorrhage with PLT counts < 10K -Transfusion threshold |
|
|
Sites of bleeding
|
Cutaneous (petechiae [lower extremities], purpura [larger petechiae], ecchymosis [spontaneous], venipuncture sites)
Mucosal (epistaxis, menorrhagia, hemorrhagic bullae in mouth - blood blisters, gastrointestinal bleeding) Central nervous system An “ooze” rather than a “gush” |
|
|
Failure of platelet production
|
Selective megakaryocyte depression
-Rare congenital defects --May-Hegglin anomaly (low platelets and inclusion bodies in neutrophils) --Thrombocytopenia and absent radii syndrome -Drugs, chemicals, viral infections Part of general bone marrow failure -Cytotoxic drugs -Radiation -Marrow infiltration -HIV infection |
|
|
Increased consumption of platelets
|
Immune
-Autoimmune/idiopathic (ITP) -Infections: HIV, malaria -Drug-induced -Heparin (HIT) -Post-transfusional purpura Disseminated intravascular coagulation (DIC) Thrombotic thrombocytopenic purpura (TTP) |
|
|
Immune thrombocytopenic purpura
|
Acute
-Abrupt onset of bruising, petechiae, mucosal bleeding in a previously healthy person -May follow an infection, usually a nonspecific URI or GI virus -Majority recover without treatment (especially in pediatric patients) Chronic -Less responsive to therapy Pathogenesis: -Body makes antiplatelet antibodies -Macrophages in spleen clear out platelets (Fc portion of antibody engages Fc receptor on macrophage) |
|
|
Giant platelet
|
Morphology:
Platelet larger than a normal red cell. Found in: Increased platelet turnover ITP |
|
|
ITP Pathophysiology
|
ITP combines the following mechanisms:
Increased platelet destruction in the spleen -Platelets are recognized by autoantibodies that bind to PGPs -Autoantibody-covered platelets are recognized by macrophages -Macrophages internalize and degrade these platelets Impaired platelet production -eTPO is constantly being bound by platelets, resulting in lower concentrations of eTPO in the blood --There is less eTPO available to stimulate platelet production by the megakaryocytes in the bone marrow -Autoantibody binding to the megakaryocytes causes some to undergo apoptosis3 --There are fewer megakaryocytes available to produce platelets --eTPO is also lost when bound to apoptotic megakaryocytes |
|
|
ITP Treatment
|
Target the Immune System
-Steroids -Splenectomy -Immune Globulin (engage Fc receptor sites on macrophages so they don't remove platelets) Increase Platelet Production -Thrombopoietin Receptor Agonists stimulate megakaryocytes |
|
|
Drugs producing thrombocytopenia
|
Ethanol
Heparin Sulfas And many, many more |
|
|
Heparin induced thrombocytopenia
|
IgG Abs directed against heparin-platelet factor 4 complex
Suspect if platelet count falls to <100,000/ul or <50% of baseline value 5 to 15 days after heparin therapy is started Venous, arterial, and microvascular thrombosis threatens life and limb Risks: any patient on heparin, less likely with LMWH Pathogenesis: This process involves formation of macromolecular complexes among heparin, platelet factor 4 (PF4), and antibodies generated against heparin/PF4. Platelets release PF4 when they are activated by agonists such as thrombin, collagen, and heparin. The immune complexes comprising heparin, PF4, and antiheparin:PF4 antibodies can interact with platelet receptors and lead to potent platelet activation, aggregation, and thrombin generation |
|
|
TTP-Thrombotic Thrombocytopenic Purpura: clincal signs and blood film
|
Devastating disorder; fatal if untreated
Clinical pentad (FAT RN): -Fever -Anemia -Thrombocytopenia -Renal dysfunction -Neurologic deficits Blood film: schistocytes + few platelets |
|
|
Pathophysiology of TTP
|
The absence or impairment (usually autoimmune) of ADAMTS13 (VWF cleaving enzyme) allows for the persistence of the ultralarge “sticky” forms of VWF, which trap platelets and cause thrombi in vessels, thus leading to end-organ damage, and the appearance of the pentad of clinical features.
|
|
|
Contraindications to platelet transfusion
|
TTP and HIT
|
|
|
Thrombocytopenia due to dilution
|
Massive transfusion
-Thrombocytopenia occurs in patients receiving massive transfusions (10-20 units) of PRBCs over a brief time frame due to the absence of viable platelets in stored PRBCs |
|
|
Platelet distribution
|
Normal:
30% in spleen 70% circulating During moderate or massive splenomegaly up to 90% of platelets can be in spleen |
|
|
Pseudothrombocytopenia
|
Counter misses if there is a clot or aggregated platelets in specimen
|
|
|
Primary hemostasis (again)
|
Platelet thrombus formation requires adequate numbers of platelets, platelet activation, and platelet interaction with both the vessel wall and other platelets In response to tissue injury, platelets adhere to areas of damage through specific receptors, the most important of which is GP Ib/IX, the von Willebrand factor receptor.
In response to signals generated by these receptors, platelets undergo a change in shape and secrete the contents of their granules. Secretion results in additional platelet stimulation, primarily through the ADP receptor. Stimulation of platelets also leads to activation of the fibrinogen receptor, glycoprotein IIb/IIIa, rendering it able to bind fibrinogen. Fibrinogen bridges glycoprotein IIb/IIIa receptors on different platelets, causing aggregation. Following stimulation, the surface of the platelet also becomes a site for activation of the protein clotting cascade, leading to the formation of fibrin. |
