Haemostasis Flashcards
Describe platelets.
- Produced in bone marrow by fragmentation of the cytoplasm of megakarocytes.
- Their main function is to form plugs during the haemostatic response to vascular injury (adhesions, aggregation and release reactions and amplification).
- non-nucleated biconvex disc
- have adhesive and contractile properties
Thrombopoietin is high in patients with thrombocytopenia cuz of marrow aplasia but low in people with raised platelet counts. T or F.
T
note: thrombopoietin is made in the liver and is used to regulate platelet formation and is removed by binding to c-MPL receptors on platelets.
Platelets aggregate with each other and adhere to the vessel endothelial wall. T or F.
T
note: both partly mediated by vWf
Adhesion to collagen is facilitated by?
Glycoprotein Ia (GPIa) & GPIb (i think)
Glycoproteins Ib, IIb/IIIa are important for?
- Attachment of platelets to von Willebrand factor (VWF), and thus to the vascular subendothelium/vessel wall.
- The binding sites for GPIIb/IIIa are also found on fibrinogen, which is important for platelet aggregation.
Primary activation of platelets leads to?
alpha granules release contents (clotting factors, VWF, platelet-derived growth factors, other proteins) leading to platelet aggregation.
What is thromboxane A2 (TXA2)?
- involved in secondary amplification of platelet activation for platelet aggregation;
- it lowers platelet cAMP (causing high Ca2+ levels) and initiates the release reactions;
- also a powerful vasoconstrictor.
what is prostacyclin (PGI2)
- inhibits platelet aggregation/primary hemostasis by increasing platelet cAMP (causing low Ca2+ levels);
- this is for when the vascular endothelium is intact/there’s no injury.
- note: other inhibitors include NO and ectonucleotidase (CD39) and aspirin; these promote vasodilation and inhibits platelet aggregation
Thrombin’s role?
- Converts fibrinogen to fibrin (enmeshes the platelet aggregates at site of injury and converts the primary plug to a firm, stable, hemostatic plug)
- note: the pathways will work to convert prothrombin to thrombin.
- the initial phase, in the extrinsic pathway, will produce small amounts of thrombin which amplifies a larger production, in the intrinsic pathway.
Coagulation is initiated after?
- Vascular injury by interaction of tissue factor (TF) with plasma factor VII.
- The TF-VIIa complex (extrinsic factor Xase) activates factors IX and X (extrinsic pathway).
- Factor X by itself, not activated will make a small amount of thrombin (that will enhance a larger production)
- The Xa-Va complex will convert prothrombin to thrombin (common pathway)
The extrinsic pathway?
- The initiation pathway which involves tissue factor;
- the formation of extrinsic Xase (TF-VIIa) initiates the coagulation cascade.
- Inhibited by tissue factor pathway inhibitor (TFPI).
- Also its predominant in-vivo.
- TF + VII –> IXa & Xa
Intrinsic pathway?
- thrombin from extrinsic pathway will initiate intrinsic factors.
- The amplification pathway/ contact activation pathway.
- Predominant in-vitro.
- intrinsic Xase is formed by IXa + VIIIa, in the presence of Ca2+ it activates enough Xa (which combines with Va) to generate thrombin.
- V and VIII are converted to Va and VIIIa (Va combines with Xa & VIIIa combines with IXa)
Factor XI deficiency causes bleeding. T or F.
T; apparently this is haemophilia C and its just mild bleeding; not major and its rare
The activity of factors II, VII, IX and X depend on what?
Vitamin K
note: coumarin is a vit K antagonist
Thrombosis?
occlusions of blood vessels (unchecked, blood coagulation could cause this)
Tissue factor pathway inhibitor (TFPI) inhibits what?
the main in vivo pathway by inhibiting factors Xa and VIIa/ the extrinsic pathway.
Protein C does what?
- destroys the activated factors V and VIII which inhibits coagulation;
- activated by thrombin-thrombomodulin complex (thrombin binds to thrombomodulin);
- it is enhanced by protein S;
- activated protein C enhances fibrinolysis; natural fibrinolytic
- note: a vit K dependent serine protease
Other inhibitors of secondary hemostasis besides TFPI?
- Antithrombin III
- heparin
theres more cant bother
Tissue plasminogen activator (TPA)?
- Converts plasminogen to plasmin, and plasmin will break down fibrin, fibrinogen, factors V and VIII into soluble fragments.
- inactivated by plasminogen activator inhibitor (PAI).
what are some fibrinolysis/tertiary hemostasis inhibitors? hint:3
- PAI (plasminogen activator inhibitor)
- alpha 2 antiplasmin
- TAFI (thrombin activated fibrinolytic inhibitor )
Ca2+ dependent reactions?
Formation of Xa
Formation of thrombin
Give egs of anticoagulants.
- EDTA, citrate- chelate Ca2+; used in vitro cuz Ca2+ needed for other reactions
- Heparin- inhibit clotting enzymes, activates antithrombin III (in secondary hemostasis); used in vivo n in vitro; monitored by PTT time
- Fluoride- inhibits glycolysis
- Coumarin- vitamin K antagonist; used in vivo; monitored by PT time
Normal platelet count?
150/250-400 x 10^9
Patients with suspected bleeding disorders like thrombocytopenia should initially have what?
a complete blood count, including a platelet count and blood film examination.
Prothrombin time (PT) measures what?
- measures EXTRINSIC and COMMON pathway factor activity 1, 2, 5, 7 & 10)
Activated partial thromboplastin time (APTT) measures what?
- Measures the intrinsic (7, 9, 11 & 12) and common pathway factors (1, 2, 5 &10)
- Measures the clotting time of plasma after the activation of contact factors but without added tissue thromboplastin.
Thrombin (clotting) time (TT) measures what?
- Measures fibrinogen function.
- TT is sensitive to fibrinogen deficiency and inhibition of thrombin
Heparin does what and is used for what?
- enhances antithrombin III by binding to it which will inactive clotting factors like Xa, IXa, XIa, XIIa, protein C and S.
- to inactivate thrombin, heparin has to bind to both antithrombin III and thrombin. LMWH isn’t long enough to bind to both.
- affects the intrinsic pathway
- used for DVT, PE, and arterial thromboembolism; may also be used in hip/knee replacement surgery
