Mucocutaneous Hemorrhage

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/coagulationHemostasis/coagulation is the body's norm

al 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 resu

lting in fibrin formation

Primary and secondary hemostasis are closely linked

Vessel wall

Blood platelets

Coagulation factors

anti-coagulation substances

fibrinolysisHemostasis coagulation

Etiology & Pathogenesis

Vessel wall disorders Abnormalities of blood platelets — Quantitative platelets defects — Qualitative platelets defects Disturbance of coagulation in circula

tion — Deficiency of coagulation factors Increase of anti-coagulation substances Hyperfunction of fibrinolysis( 纤维蛋白溶解 )

Defects on the vessel wall

Capillaries are made only of endothelium

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 subendotheli

al matrix Defect of extravascular connective tissues t

hat 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

excess production of glucocorticoids

develop generalized protein wasting

atrophy of the supporting connective tissue around blood vessels

skin bleeding or easy bruising

Cushing's syndrome

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.

Abnormalities of blood platelets

Blood platelets function in primary hemostasis platelet adhesion and aggregation

Platelet activation from thromboxane A 2 fur

ther 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.

Red blood

cell Blood platelet

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 thrombocytopeni

a( 血小板减少症 ) with various causes

Qualitative platelets defects — Platelets dysfunction, as thromba

sthenia( 血小板无力 )

Causes of thrombocytopenia

Primary thrombocytopenia Immunologic thrombocytopenia(vir

al or bacterial infections) Drug-induced thrombocytopenia Hypersplenia( 脾功能亢进 ) Aplastic anemia( 再生障碍性贫血 ), le

ukemia( 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.

Deficiency of coagulation factors

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 hepatocellula

r 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

Fibrinolytic system

( 纤溶酶原 )

( 纤溶酶 )

( 纤溶系统 )

Defects in the fibrinolytic system a2 plasmin inhibitor deficiency or plasmi

nogen 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 fluct

uation Epistaxis( 鼻出血 ) Bleeding in skin, mucous membrane, joint

cavity and viscera( 内脏 ).

Petechiae

Purpura

Ecchymosis (Bruise)

Hematoma

Approach to patients with mucocutaneous hemorrhag

e

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 bleedin

g 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 tissue

s, 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 plat

elet function) Prothrombin time (PT, screens the extrin

sic limb of the coagulation system) Coagulation time

Bone marrow studyCoagulation factors determinationFibrinogen determination.

Screening tests

Specific tests