Haematology - Physiology Flashcards
What is the blood group of an individual with the A antigen on red blood cells and B antibody in plasma?
Group A
What is the blood group of an individual with the B antigen on red blood cells and A antibody in plasma?
Group B
What is the blood group of an individual with both A and B antigens on red blood cells?
Group AB (universal recipient)
What is the blood group of an individual with neither A nor B antigens on red blood cells and both A and B antibodies in plasma?
Group O (universal donor)
What is the blood type of an individual who is a universal recipient of blood cells?
Blood group AB; A and B antigen on red blood cells
What is the blood type of an individual who is a universal donor of blood products?
Blood group O; neither A nor B antigens on red blood cells
A patient receiving a blood transfusion suddenly develops symptoms of anaphylaxis, renal failure, and hypotension and has schistocytes on a smear; what is the likely cause?
Incompatible blood type transfusion
What happens when an Rh-negative mother is exposed to Rh-positive blood (for instance, during delivery)?
Exposure to Rh-positive blood (which has the Rho antigen) will result in the development of anti-Rh immunoglobulin G antibodies, which may complicate future pregnancies
Which class of antibodies are produced against the ABO blood groups?
Immunoglobulin M
Which class of antibodies are produced against Rh factor?
Immunoglobulin G
If a mother is blood type O and her fetus is blood type B, will the fetus be at risk for hemolytic disease of the newborn?
No; antibodies against ABO blood groups are immunoglobulin M class and do not cross the placenta
What happens when an Rh-negative mother with anti-Rh antibodies becomes pregnant with a child who is Rh positive?
Erythoblastosis fetalis; the anti-Rh immunoglobulin G crosses the placenta and causes hemolysis in the newborn
What part of the fibrinolytic system also activates the complement cascade by cleaving C3 to C3a?
Plasmin
Kallikrein links the coagulation cascade to the kinin cascade through its activation of _____ and to the fibrinolytic system through its activation of _____.
Bradykinin; plasminogen (to plasmin)
Name two reactions initiated by high-molecular-weight kininogen.
High-molecular-weight kininogen is the initial reagent in the kinin cascade and stimulates the coagulation cascade by interacting with factor XII
What does plasmin create when it interacts with fibrin clots?
Fibrin split products (fibrin degradation)
Once high-molecular-weight kininogen cleaves to form bradykinin, what are the effects of the kinin cascade?
Vasodilation, vascular permeability, and pain
What factor converts prokallikrein to kallikrein and factor XI to XIa?
Factor XIIa; it is thus involved in both the kinin cascade and the coagulation cascade
Which coagulation factors are specific to the intrinsic coagulation pathway?
Factor XII, factor XI, factor IX, and factor VIII
Which coagulation factors are specific to the extrinsic coagulation pathway?
Factor VII and tissue factor (thromboplastin)
Which coagulation factors are common to both the intrinsic and extrinsic coagulation pathways?
Factor X, factor V, factor II (prothrombin), and factor XIII
What is the end result of the coagulation cascade?
The conversion of fibrinogen into fibrin to form a fibrin mesh that will stabilize the platelet plug
Which reactions in the coagulation cascade require calcium and a phospholipid surface as cofactors?
The conversion of factor IX to IXa, VII to VIIa, X to Xa, and II to IIa
What are two stimuli for the conversion of factor X to factor Xa?
Activated factor VIIa, or factor IXa with factor VIIIa as a cofactor; this is where the intrinsic and extrinsic pathways converge
Which four reactions is thrombin involved in?
Thrombin (IIa) cleaves fibrinogen into fibrin monomers, activates factor XIII to help stabilize and cross-link the fibrin mesh, and activates both factor VIII and factor V
What ion does factor XIII require to stabilize the fibrin mesh?
Calcium
Why do susceptible individuals develop angioedema when taking an angiotensin-converting enzyme inhibitor?
Angiotensin-converting enzyme deactivates bradykinin; blocking this results in the unopposed activation of bradykinin by kallikrein
Name two initiators of the intrinsic coagulation pathway.
Factor XII is converted to XIIa in the presence of endothelial damage (collagen basement membrane and activated platelets) and by high-molecular-weight kininogen
What disorder results from a deficiency of factor VIII?
Hemophilia A
What disorder results from a deficiency of factor IX?
Hemophilia B
A patient is severely deficient in vitamin K; which coagulation factors will be affected?
This will result in decreased levels of factors II, VII, IX, X, and proteins C and S
What reaction accounts for the effects of heparin?
Heparin activates antithrombin, resulting in inhibition of thrombin and factors IXa, Xa, XIa, and XIIa
Name four mediators of thrombus formation or degradation that are found within the vascular endothelial cell.
von Willebrand;s factor, thromboplastin, tissue plasminogen activator, and prostaglandin I2
Which molecule, found on the surface of vascular endothelial cells, is a cofactor in the activation of protein C, an anticoagulant?
Thrombomodulin, which is located on the surface of vascular endothelial cells
Which molecule binds the subendothelial collagen that is exposed after endothelial damage?
von Willebrand;s factor binds to the subendothelial collagen and attaches to activated platelets
Via which molecule does von Willebrand;s factor attach to platelets?
von Willebrand;s factor binds to glycoprotein Ib, found on the platelet surface membrane
What event causes expression of glycoprotein IIa/IIIb on the platelet membrane?
Upon adenosine diphosphate activation of the platelet, glycoprotein IIa/IIIb is inserted into the surface membrane
How do platelets adhere to one another?
Glycoprotein IIb/IIIa binds fibrinogen, bridging platelets together
Which contributors to thrombogenesis are found within platelets?
von Willebrand;s factor, fibrinogen, and, upon cyclooxygenase activation of the arachidonic acid cascade, thromboxane A2
What is the difference between the function of glycoprotein Ib and glycoprotein IIb/IIIa on the platelet surface?
Glycoprotein Ib binds von Willebrand;s factor on a damaged endothelial surface, whereas glycoprotein IIa/IIIb binds fibrinogen attached to other platelets
What process occurs during the adhesion stage of platelet plug formation?
The platelet adheres to exposed subendothelial collagen via glycoprotein Ib and von Willebrand;s factor
Which product of the arachidonic acid pathway favors aggregation of platelets? Which molecules inhibit aggregation?
Thromboxane, which is released by platelets, is proaggregation; prostacyclin and nitric oxide, released by endothelial cells, are antiaggregation
How does aspirin prevent clot formation?
Aspirin inhibits cyclooxygenase in the platelets, thereby preventing TxA2formation and thus aggregation of platelets
What occurs during the swelling stage of platelet plug formation?
The platelet plug swells as many platelets bind together secondary to adenosine diphosphate activation of glycoprotein IIa/IIIb bridge formation
Which ion helps to strengthen the platelet plug once it has formed?
Calcium
Which stage of platelet plug formation is affected by ticlopidine and clopidogrel?
Swelling; these drugs inhibit the adenosine diphosphate-induced expression of glycoprotein IIa/IIIb
Which medication directly interferes with glycoprotein IIa/IIIb?
Abciximab
What enzyme is involved in vitamin K activation?
Epoxide reductase
How does warfarin act as an anticoagulant?
It inhibits epoxide reductase, thereby inhibiting the activation of vitamin K
Why do neonates receive an injection of vitamin K soon after birth?
Neonates lack enteric bacteria that produce vitamin K and can therefore be deficient in the vitamin K-dependent factors and suffer hemorrhagic disease
Name three endogenous factors that initiate anticoagulation.
Antithrombin III, protein C, plasminogen
What is the role of protein S in anticoagulation?
Protein S is a cofactor for protein C activation, which inactivates factors Va and VIIIa
How does plasminogen act as an anticoagulant?
Plasminogen is activated by tissue plasminogen activator to plasmin, which cleaves the fibrin clot
What is tissue plasminogen activator used for clinically?
As a thrombolytic in cases of acute stroke or myocardial infarction within hours of clot formation; tissue plasminogen activator activates plasminogen to plasmin
What is the result of the factor V Leiden mutation?
The mutation results in a factor V that resists inactivation by activated protein C, leading to a hypercoagulable state
What is the relationship between von Willebrand;s factor and factor VIII?
von Willebrand;s factor prolongs the half-life of factor VIII, which is why there is an increase in partial thromboplastin time in severe variants of von Willebrand;s disease
