1. Mucocutaneous Hemorrhage

2. Definition
Mucocutaneous hemorrhage is caused by the abnormalities of hemostasis(止血) and /or coagulation(凝血), characterized by local or extensive mucocutaneous hemorrhage derived from capillary. The bleeding is usually spontaneous or from slight trauma.

3. Hemostasis/coagulation
Hemostasis/coagulation is the body's normal physiological response for the prevention and stopping of bleeding/hemorrhage.

4. Primary and secondary hemostasis are closely linked
Hemotasis
Primary hemostasis
---platelet plug formation at sites of injury
Secondary hemostasis
---plasma coagulation system reaction resulting in fibrin formation
Primary and secondary hemostasis are closely linked

5. Vessel wall
Blood platelets
fibrinolysis
Hemostasis coagulation
Coagulation
factors
anti-coagulation substances

6. Etiology & Pathogenesis
Vessel wall disorders
Abnormalities of blood platelets
— Quantitative platelets defects
— Qualitative platelets defects
Disturbance of coagulation in circulation
— Deficiency of coagulation factors
Increase of anti-coagulation substances
Hyperfunction of fibrinolysis(纤维蛋白溶解)

7. Defects on the vessel wall

8. Capillaries are made only of endothelium

9. Constriction of capillary playing the role of hemostasis
local vascular constriction
sealing the damaged vascular endothelium
reducing blood flow

10. Vascular wall disorders
Damage to capillary endothelium
Abnormalities in the vascular subendothelial matrix
Defect of extravascular connective tissues that support blood vessels
Formation of abnormal blood vessels.

11. Defects on Capillary Wall
Hereditary
Telangioectasia(毛细血管扩张);
Acquired
Allergic purpura(过敏性紫癜);
Senile purpura
Non- thrombocytopenic purpura
— Severe infection
— Vitamin C deficiency
— Uremia

12. Vitamin C is needed to synthesize hydroxyproline(羟脯氨酸), an essential constituent of collagen

13. Cushing's syndrome excess production of glucocorticoids
develop generalized protein wasting
atrophy of the supporting connective tissue around blood vessels
skin bleeding or easy bruising

14. Ageing causes a similar atrophy of perivascular connective tissues
Senile purpura
Ageing causes a similar atrophy of perivascular connective tissues

15. In this situation,BT and CT are normal,but capillary fragility test is positive.

16. Abnormalities of blood platelets

17. Blood platelets function in primary hemostasis
platelet adhesion and aggregation
Platelet activation from thromboxane A further aggregates platelets (to form the white thrombus ) and enhances vasoconstriction
platelet secretion activated platelets secrete platelet agents, 5-HT and coagulators participating in the coagulation process and facilitate the clot constriction.

18. Blood platelet
Red blood cell

19. Some of the products secreted by platelets are depicted as:
ADP, adenosine diphosphate(腺苷二磷酸);
PDGF, platelet-derived growth factor(血小板源性生长因子);
vWF, von Willebrand factor.

20. arachidonic acid(花生四烯酸); cyclooxygenase(环氧合酶); endoperoxide(内皮过氧化酶);
Generation of thromboxane A2 in platelets and prostacyclin (PGI2) in endothelial cells.
arachidonic acid(花生四烯酸);
cyclooxygenase(环氧合酶);
endoperoxide(内皮过氧化酶);
thromboxane(血栓素);
prostacyclin(前列环素);

21. Abnormalities of Blood Platelets
Quantitative platelets defects
— BPC is low, as thrombocytopenia(血小板减少症) with various causes
Qualitative platelets defects
— Platelets dysfunction, as thrombasthenia(血小板无力)

23. Causes of thrombocytopenia
Primary thrombocytopenia
Immunologic thrombocytopenia(viral or bacterial infections)
Drug-induced thrombocytopenia
Hypersplenia(脾功能亢进)
Aplastic anemia(再生障碍性贫血), leukemia(白血病)

24. Functional platelet disorders
Congenital :
Thrombasthenia
Giant platelet syndrome(巨大血小板综合征)
Acquired :
Liver disease
Uremia
Drug-induced

25. In platelet defects,bleeding time is prolonged and clot retraction is poor.

26. Deficiency of coagulation factors

27. Coagulation process
First stage :the formation of activated thrombokinase(凝血酶原激酶).
Second stage:thrombokinase converts prothrombin(凝血酶原) into thrombin(凝血酶).
Final stage: thrombin in turn converts fibrinogen(纤维蛋白原) into fibrin(纤维蛋白).

29. Congenital plasma coagulation defects
Hemophilia A-dificiency of factor VIII
Hemophilia B-dificiency of factor IX
Hemophilia C-dificiency of factor XI
Deficiencies in factors V, VII, X, and prothrombin (factor II)

30. Acquired coagulation disorders
Vitamin K deficiency(II, VII,IX, X)
Liver disease
Disseminated intravascular coagulation (DIC)
Complications of anticoagulant therapy

31. Vitamin K deficiency
Serves as a cofactor in the enzymatic carboxylation of glutamic acid(谷氨酸) residues on prothrombin complex proteins (factors II, VII, IX, X; proteins C and S)
Plasma levels of all the prothrombin complex proteins decrease.

32. Vitamin K Deficiency Inadequate dietary intake
Intestinal mal-absorption
Loss of storage sites due to hepatocellular disease

33. Coagulation Disorders in Liver Disease
Decreased production of coagulation proteins(II,VII,IX,X), and fibrinogen(factor I) and factor V
Some degree of vitamin K deficiency
“Hypercoagulable" and predisposed to developing DIC or systemic fibrinolysis.

34. Lab test of coagulation defectPT
PTT CT
platelet count
fibrinogen determination

35. Fibrinolytic system

36. (纤溶系统)
(纤溶酶原)
(纤溶酶)

38. Defects in the fibrinolytic system
a2 plasmin inhibitor deficiency or plasminogen activator inhibitor (PAI) 1
Secondary fibrinolysis accompanying DIC

39. Increase of anti-coagulation substances
the increase of heparan anticogulants or the over-dosage of anticoagulants.

40. Types of Mucocutaneous hemorrhage
Petechia(出血点;瘀点): pinpoint hemorrhage
<2mm in diameter
Purpura(紫癜): > 3- 5mm in diameter
Ecchymosis(瘀斑): common bruise, >5mm
Hematoma(血肿): local elevation and fluctuation
Epistaxis(鼻出血)
Bleeding in skin, mucous membrane, joint cavity and viscera(内脏).

41. Petechiae
Ecchymosis (Bruise)
Hematoma
Purpura

42. Approach to patients with mucocutaneous hemorrhage

43. History-taking Age,male or female,onset of the disease
Spontaneous or following trauma
Past history of bleeding tendency, such as bleeding after tooth extraction,
Liver disease
A family history of bleeding and bleeding from multiple sites, repeated episodes
A record of drug ingestion

44. Physical examination
Bleeding should be traced over whole body, sometimes including urine and stool.
In addition, the jaundice and the size of liver and spleen should be noted.

45. Bleeding from a platelet disorder
Bleeding sites localized to superficial sites such as the skin and mucous membranes
Immediately after trauma or surgery
Readily controlled by local measures

46. Bleeding from plasma coagulation defects
Bleeding sites: in deep subcutaneous tissues, muscles, joints, or body cavities
time: hours or days after injury
Unaffected by local therapy

47. Laboratory routine tests
Blood routine
Blood platelet count
Bleeding time (a sensitive measure of platelet function)
Prothrombin time (PT, screens the extrinsic limb of the coagulation system)
Coagulation time
Bone marrow study
Coagulation factors determination
Fibrinogen determination.
Screening tests
Specific tests