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.
Hemostasis/coagulation Hemostasis/coagulation is the body's normal physiological response for the prevention and stopping of bleeding/hemorrhage.
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
Vessel wall Blood platelets fibrinolysis Hemostasis coagulation Coagulation factors anti-coagulation substances
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)
Constriction of capillary playing the role of hemostasis local vascular constriction sealing the damaged vascular endothelium reducing blood flow
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.
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
Vitamin C is needed to synthesize hydroxyproline(羟脯氨酸), an essential constituent of collagen
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
Senile purpura Ageing causes a similar atrophy of perivascular connective tissues
In this situation,BT and CT are normal,but capillary fragility test is positive.
Blood platelets function in primary hemostasis • platelet adhesion and aggregation • Platelet activation from thromboxane A2further 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.
Blood platelet Red blood cell
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.
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);
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)
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)
Functional platelet disorders Congenital : • Thrombasthenia • Giant platelet syndrome(巨大血小板综合征) Acquired : • Liver disease • Uremia • Drug-induced
In platelet defects,bleeding time is prolonged and clot retraction is poor.
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).
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)
Acquired coagulation disorders • Vitamin K deficiency(II, VII,IX, X) • Liver disease • Disseminated intravascular coagulation (DIC) • Complications of anticoagulant therapy
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.
Vitamin K Deficiency • Inadequate dietary intake • Intestinal mal-absorption • Loss of storage sites due to hepatocellular disease
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.
Lab test of coagulation defect • PT • PTT • CT • platelet count • fibrinogen determination
(纤溶系统) (纤溶酶原) (纤溶酶)
Defects in the fibrinolytic system • a2 plasmin inhibitor deficiency or plasminogen activator inhibitor (PAI) 1 • Secondary fibrinolysis accompanying DIC
Increase of anti-coagulation substances the increase of heparan anticogulants or the over-dosage of anticoagulants.
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).
Petechiae Ecchymosis (Bruise) Hematoma Purpura
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
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.
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
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
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