What are the most abundant integral proteins and what is an important characteristic?
(1) Glycophorins, (2) which contain sialic acid that gives the cell surface a negative charge to repel other RBCs
What are band 3 proteins?
(1) Anion transporters that are (2) associated with ABO and Rh antigens
What are four proteins that form the cytoskeleton?
(1) Spectrin (2) Ankyrin (3) Actin (4) Band 4.1/4.2
How does the RBC generate ATP?
Embden-Myerhoff Pathway (EMP)
Which reactions does the Embden-Myerhoff Pathway allow to occur?
(1) Hexose monophosphate pathway - detoxify oxidants
(2) Methemoglobin reductase pathway - reduce oxidized Hb
(3) Rapoport-Leubering pathway - generates 2,3-BPG to promote release of oxygen from hemoglobin
What chains comprise HbF, HbA, and HbA2?
HbF - α2γ2 (up to 90% at birth) HbA - α2β2 (95% after 2 years of age) HbA2 - α2δ2 (
Where are the two largest stores of iron in the body?
(1) Hemoglobin and (2) ferritin
What receptor determines the amount of iron entering a cell?
Transferrin receptor (TfR)
What are the four steps in primary hemostasis?
(1) Transient vasoconstriction mediated by (a) neural stimulation and (b) endothelin release from endothelial cells (2) Von Willebrand factor attaches to exposed collagen at site of injury and platelets bind to VWF by GPIb receptor (3) Attached platelets degranulate, releasing (a) ADP, which promotes exposure of GPIIb/IIIa receptor and (b) thromboxane A2 synthesized by platelet cyclooxygenase (COX), promoting platelet aggregation (4) Platelets aggregate via GPIIb/IIIa, using fibrinogen as a linker molecule
Where is Von Willebrand factor found?
(1) Plasma (2) α-granules of platelets (3) Weibel-Palade bodies in endothelial cells
What cleaves Von Willebrand factor multimer?
What four things does Von Willebrand factor bind?
(1) Collagen (2) GPIb (3) GPIIb/IIIa (mediates platelet aggregation) (4) Factor VIII (protects F8 from proteolysis)
Which clotting factors are dependent on vitamin K?
Factors II, VII, IX, X
What are four major inhibitors of coagulation?
(1) Antithrombin - inhibits IIa, IXa, Xa, XIa (2) Activated protein C - inactivates Va and VIIIa (3) Protein Z-dependent protease inhibitor - inhibits Xa (4) Tissue factor pathway inhibitor - Binds Xa and prevents further activation by TF-VIIa
What causes thrombotic thrombocytopenic purpura?
Decreased ADAMTS13, leading to microthrombi
What are the activators of fibrinolysis?
(1) Tissue plasminogen activator (TPA) (2) Urokinase plasminogen activator (UPA)
What inhibits plasmin?
α2-antiplasmin - binds free plasmin to prevent digestion of coagulation factors
Where does D-dimer come from?
(1) Lysis of fibrin, (2)not fibrinogen by (3) plasmin Elevated in DIC, not in plasmin overactivity (because fibrinogen degraded)
What inhibits TPA and UPA?
Plasminogen activator inhibitor 1
What are PT, APPT, and TCT?
(1) PT - prothrombin time (extrinsic pathway) (2) APPT Activated partial thromboplastin time (intrinsic pathway) (3) Thrombin clotting time (fibrinogen to fibrin)
When is PT prolonged?
When factors I, II, V, X, or VII are deficient
When is APPT prolonged?
When factors I, II, V, X, VIII, IX, XI, or XII are deficient
When is TCT prolonged?
Deficiency of factor I (fibrinogen)
Which coagulation factors cause no bleeding if deficient?
(1) Factor XII (2) Prekalikrein (PK) (3) High molecular weight kininogen (HK)
What are the three types of mucocutaneous bleeding of the skin and how are they classified?
(1) Petechiae (1 mm diameter) (2) Purpura (3 mm diameter) (3) Ecchymoses (1 cm diameter)
What are three disorders of primary hemostasis?
(1) Thrombocytopenia (2) Functional platelet defects (3) Von Willebrand Disease
What is normal platelet count? Thrombocytopenia?
Normal range: 150,000-450,000 Thrombocytopenia:
What are two major categories of causes of thrombocytopenia?
(1) Decreased production (congenital or acquired) (2) Increased destruction (immune, microangiopathic)
What is the mechanism of immune thrombocytopenic purpura?
(1) Formation of autoantibody to GPIIa/IIIb (2) Acute form in children, usually after viral infection or immunization (self-limiting) (3) Chronic form more common in adults, especially women
What is the mechanism of neonatal alloimmune thrombocytopenia?
Mother forms IgG alloantibody that binds to fetal platelets
What is the mechanism of heparin-induced thrombocytopenia?
(1) Heparin binds platelet factor 4 (PF4), (2) forming heparin-PF4 complexes (3) to which the patient develops IgG antibody (4) leading to platelet aggregation and thrombosis
What are three types of thrombotic microangiopathies?
(1) Thrombotic thrombocytopenic purpura (2) Hemolytic uremic syndrome (3) Disseminated intravascular coagulation
How does TTP occur?
(1) Acquired autoantibody to ADAMTS-13, a protein that cleaves vWF (2) Secondary TTP resulting from stem cell transplant, pregnancy, HIV, drugs (3) Lack of functional ADAMTS-13 leads to ultra-large vWF, which spontaneously binds GPIb, causing thrombosis
What is the triad/pentad involved in TTP?
(1) Thrombocytopenia (2) Microangiopathic hemolytic anemia (3) Neurological symptoms (distinguishes TTP from HUS) (4) Fever (5) Renal failure
What is the triad of HUS?
(1) Thrombocytopenia (2) Microangiopathic hemolytic anemia (3) Renal failure (Distinguishes HUS from TTP)
What are the lab values in DIC?
(1) Increased PT, aPPT, TCT (2) Decreased fibrinogen (3) Decreased platelets (4) Increased D-dimer (product of cross-linked fibrin breakdown) (5) Microangiopathic hemolytic anemia (6) Schistocytes on blood smear
Where are defects in functional platelet disorders?
(1) Adhesion (GPIb)
(2) Aggregation (GPIIb/IIIa)
(3) Secretion (defective generation of TXA2)
(4) Abnormal α granules
What is Bernard Soulier Syndrome (BSS)?
(1) Autosomal recessive functional platelet disorder in which (2) a mutation results in a defective GPIb receptor leading to (3) thrombocytopenia and (4) giant platelets
What is Glanzmann Thrombasthenia?
(1) An autosomal recessive disoder in which (2) a mutation leads to defective GPIIb/IIIa, with (3) normal platelet count
What is von Willebrand disease?
What are lab values for platelet count, bleeding time, PT, aPPT, and TCT?
(1) A congenital bleeding disorder in which there is (2) deficient or defective vWF
Bleeding time: increased
aPPT: elevated because vWF stabilizes Factor VIII
How is von Willebrand disease diagnosed?
(1) Abnormal riscocetin test: riscocetin causes vWF to bind GPIb, leading to agglutination - if no agglutination, abnormal test
(2) vWF antigen
(3) Factor VIII activity
What are two days von Willebrand disease is treated?
(1) Desmopressin acetate, which causes release of vWF from Weibel-Palade bodies of endothelial cells
(2) vWF-FVIII concentrate
What is the cause of hemophilia A?
(1) Autosomal recessive (2) Factor VIII deficiency
What is the cause of hemophilia B? What is another name for the disease?
(1) Autosomal recessive (2) Factor IX deficiency
(3) Christmas disease
When PT and TCT are normal but aPPT are prolonged, what should the interpretation be if a mixing study corrects the aPPT? If it does not?
(1) If bleeding, Factor VIII, IX, XI deficiency
(2) If not bleeding, Factor XII, prekallikrein, high molecular weight kininogen deficiency
(3) If bleeding, factor-specific antibodies
(4) If not bleeding, lupus anticoagulant
What are lupus anticoagulants?
(1) Antiphospholipid antibodies that (2) increase aPPT (3) but cause no bleeding and (4) occur in response to infections or certain drugs
What results from vitamin K deficiency?
(1) No γ-carboxylation of glutamic acids of Factors II, VII, IX, and X
(2) Increased PT and aPPT
(3) Normal TCT
(4) Decreased activity of Factors II, VII, IX, and X
(5) Factor VII decreases first because of short half life
What are fibrinolysis disorders and what are three causes?
(1) Premature degradation of fibrin leading to systemic or localized bleeding with (2) increased PT, aPPT, and TCT
Inherited deficiency of (3) plasminogen activator inhibitor, (4) α2-antiplasmin, or (5) acquired systemic hyperfibrinolysis
What are four functions of thrombin?
(1) Fibrinogen activation to fibrin
(2) Platelet aggregation
(3) Endothelium activation to produce anti-clotting factors (NO, PGI2, tPA)
(4) Leukocyte activation
What is Virchow's Triad?
(1) Three factors that cause thrombosis:
(2) Endothelial injury
(3) Abnormal blood flow
What are five hypercoagulable states?
(1) Coagulation factors (ex. Factor V Leiden
(2) Deficient thrombolytic factors (ex. tPA deficiency)
(3) Antiphospholipid antibodies (Lupus anticoagulant)