Mucocutaneous Hemorrhage
Definition Mucocutaneous hemorrhage is caused by the abnormalities of hemostasis() and /or coagulation(), 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 normal physiological response for the prevention and stopping of bleeding/hemorrhage.
HemotasisPrimary hemostasis---platelet plug formation at sites of injurySecondary hemostasis---plasma coagulation system reaction resulting in fibrin formationPrimary and secondary hemostasis are closely linked
Vessel wallBlood plateletsCoagulation factorsanti-coagulation substances
fibrinolysisHemostasis coagulation
Etiology & PathogenesisVessel wall disordersAbnormalities of blood platelets Quantitative platelets defects Qualitative platelets defects Disturbance of coagulation in circulation Deficiency of coagulation factorsIncrease of anti-coagulation substancesHyperfunction of fibrinolysis()
Defects on the vessel wall
Capillaries are made only of endothelium
Constriction of capillary playing the role of hemostasis
local vascular constrictionsealing the damaged vascular endothelium reducing blood flow
Vascular wall disorders Damage to capillary endotheliumAbnormalities in the vascular subendothelial matrix Defect of extravascular connective tissues that support blood vesselsFormation of abnormal blood vessels.
Defects on Capillary Wall Hereditary Telangioectasia();
Acquired Allergic purpura(); Senile purpura Non- thrombocytopenic purpura Severe infection Vitamin C deficiency Uremia
Vitamin C is needed to synthesize hydroxyproline(), 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 bruisingCushing's syndrome
Senile purpuraAgeing 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 hemostasisplatelet adhesion and aggregation
Platelet activation from thromboxane A 2 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.
Red blood cell Blood platelet
Some of the products secreted by platelets are depicted as:ADP, adenosine diphosphate();PDGF, platelet-derived growth factor(); vWF, von Willebrand factor.
Generation of thromboxane A2 in platelets and prostacyclin (PGI2) in endothelial cells.arachidonic acid();cyclooxygenase();endoperoxide();thromboxane();prostacyclin();
Abnormalities of Blood PlateletsQuantitative platelets defects BPC is low, as thrombocytopenia() with various causes
Qualitative platelets defects Platelets dysfunction, as thrombasthenia()
Causes of thrombocytopenia
Primary thrombocytopeniaImmunologic thrombocytopenia(viral or bacterial infections)Drug-induced thrombocytopeniaHypersplenia() Aplastic anemia(), leukemia()
Functional platelet disordersCongenital : ThrombastheniaGiant platelet syndrome()Acquired :Liver diseaseUremiaDrug-induced
In platelet defects,bleeding time is prolonged and clot retraction is poor.
Deficiency of coagulation factors
Coagulation processFirst stage :the formation of activated thrombokinase(). Second stage:thrombokinase converts prothrombin() into thrombin(). Final stage: thrombin in turn converts fibrinogen() into fibrin().
Congenital plasma coagulation defects Hemophilia A-dificiency of factor VIIIHemophilia B-dificiency of factor IXHemophilia C-dificiency of factor XIDeficiencies in factors V, VII, X, and prothrombin (factor II)
Acquired coagulation disorders Vitamin K deficiency(II, VII,IX, X)Liver diseaseDisseminated intravascular coagulation (DIC)Complications of anticoagulant therapy
Vitamin K deficiencyServes as a cofactor in the enzymatic carboxylation of glutamic acid() 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 DeficiencyInadequate dietary intake Intestinal mal-absorptionLoss of storage sites due to hepatocellular disease
Coagulation Disorders in Liver DiseaseDecreased production of coagulation proteins(II,VII,IX,X), and fibrinogen(factor I) and factor V Some degree of vitamin K deficiencyHypercoagulable" and predisposed to developing DIC or systemic fibrinolysis.
Lab test of coagulation defectPTPTTCTplatelet countfibrinogen determination
Fibrinolytic system
()()()
Defects in the fibrinolytic system a2 plasmin inhibitor deficiency or plasminogen activator inhibitor (PAI) 1 Secondary fibrinolysis accompanying DIC
Increase of anti-coagulation substancesthe increase of heparan anticogulants or the over-dosage of anticoagulants.
Types of Mucocutaneous hemorrhagePetechia(;): pinpoint hemorrhage 3- 5mm in diameter Ecchymosis(): common bruise, >5mmHematoma(): local elevation and fluctuationEpistaxis()Bleeding in skin, mucous membrane, joint cavity and viscera().
PetechiaePurpuraEcchymosis (Bruise)Hematoma
Approach to patients with mucocutaneous hemorrhage
History-takingAge,male or female,onset of the diseaseSpontaneous or following traumaPast history of bleeding tendency, such as bleeding after tooth extraction,Liver disease A family history of bleeding and bleeding from multiple sites, repeated episodesA record of drug ingestion
Physical examinationBleeding 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 disorderBleeding 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 testsBlood routine Blood platelet countBleeding time (a sensitive measure of platelet function) Prothrombin time (PT, screens the extrinsic limb of the coagulation system) Coagulation time
Bone marrow studyCoagulation factors determinationFibrinogen determination.
Screening testsSpecific tests
