1. Chapter 23. Bleeding disorders associated with coagulopathy
O bleeding
platelet count, bleeding time, capillary fragility test: normal
PT, aPTT: prolonged
-> coagulation factor, fibrinogen deficiency
O hereditary (hemophilia A, B, C, von Willebrand disease) vs acquired
01. Bleeding disorders associated with congenital coagulopathy
1. Hemophilia A
O factor VIII deficiency (reduced amount or activity)
O sex-linked recessive
O the most common coagulopathy
O severe hemophilia A: inversion
mild-moderate hemophilia A: missense mutation

2. release of blood protease into the synovial space
O clinical presentation: delayed and spontaneous nature of the bleeding
- acute hemarthrosis
release of blood protease into the synovial space
-> cartilage destruction -> joint destruction
- intramuscular hemorrhage
- central nervous system bleeding: the most common cause of death
O aPTT: prolonged
O PT, bleeding time, thrombin clotting time (TCT): normal
O specific coagulation factor assay for factor VIII
(40%)

5. O von Willebrand disease: factor VIII activity (VIII:C) -> reduced
2. Hemophilia B
O factor IX deficiency O sex-linked recessive
O clinical presentation: identical to those of hemophilia A
O aPTT: prolonged
PT, thrombin clotting time, Bleeding time: normal
specific factor assay for factor IX
3. Hemophilia C
O factor XI deficiency (activated by thrombin) O autosomal recessive
specific factor assay for factor XI

6. 4. Von Willebrand disease
O defect in vWF
O heterogenous disorder
O vWF: participates in primary hemostasis
carrier protein for factor VIII (stability)
exists as a series of oligomer (from dimer to oligomer)
synthesized in endothelial cell (Weibel-Palade body), megakaryocyte
N: VIII binding site M: collagen, GPIb-IX-V binding site (A domain)
C: GPIIb-IIIa binding site (C1 domain)
O clinical presentation: platelet-type bleeding
O lab evaluation
-bleeding time: prolonged (cf. platelet disorder, connective disorder)
-Ristocetin cofactor activity (Ristocetin-induced platelet agglutination): 감소
restocetin -> structural change of vWF -> exposing A domain
-> induce agglutination of platelet
-plasma vWF antigen
-Factor VIII activity (using aPTT)
-Multimer analysis
type I vWD: overall decreased but normal array of vWF multimers
type II vWD: abnormal multimer pattern
type III vWD: absence of all vWF multimers

9. 5. 기타 유사혈우병 질환
(1) Factor XII, prekalikrein, HMWK
O not associated with bleeding
O aPTT: prolonged
O because in vivo they do not participate in hemostasis
(2) Factor II, X, V (in common pathway)
O rare disorders
O PT, aPTT: prolonged
bleeding time, thrombin clotting time: normal
O V deficiency: parahemophilia
(3) Factor VII (in extrinsic pathway)
O isolated prolonged PT
aPTT, bleeding time, thrombin clotting time: normal
(4) Disorders of fibrinogen
O hereditary afibrinogenemia
O hereditary hypofibrinogenemia
O dysfibrinogenemia
O PT, aPTT, thrombin clotting time: prolonged
(5) Factor XIII deficiency
O PT, aPTT, thrombin clotting time, platelet count, bleeding time: normal
O Urea clot solubility test: shortened

10. 02. Acquired coagulopathy and Bleeding disorders
O cause: medication, underlying disease
1. Anticoagulant agents
O Heparin: antithrombin III -> thrombin
O warfarin (Coumadin): vitamin K antagonist -> II, X, IX, VII, protein C,S
O Low-molecular weight heparin: Xa
2. DIC
O cause bleeding (consumptional coagulopathy)
or thrombosis (혈액순환장애) -> shock, acidosis
O simultaneous presence of thrombin and plasmin
O acute DIC: hemorrhagic condition
chronic DIC: prothrombic condition
O antithrombin III, alpha2-antiplasmin: decrease
3. Liver disease
O liver: synthesize all coagulation proteins
clears plasmin

11. 4. Vitamin K deficiency
O water insoluble
O nutritionally depleted/ malabsorption (bile juice deficiency)
O warfarin
O antibiotics
5. Massive transfusion
O dilution of plasma and platelet
O increased concentrations of the anticoagulant sodium citrate
6. Uncommon acquired coagulation protein defects
O dysfibrinogenemia
O inhibitors (antibody) to coagulation factors
O hypergammaglobulinemic states (coagulation inhibition)
O malignancy: produce heparinoids
7. Uremia (요독증)
O blood vessel damage
O coagulation deficiency
O platelet defects
8. Hyperfibrinolysis