HOW TO APPROACH TO A PATIENT WITH BLEEDING DISORDERS

EVALUATION OF THE BLEEDING PATIENT DEFINITION

Hemostasis
The arrest of bleeding from an injured blood vessel, involving the combined regulatory activity of vascular, platelet, and plasma factors

Primary Hemostasis
Vessel wall function Platelet functions of Adhesion, Aggregation

Secondary hemostasis Plasma coagulation factors leading to fibrin deposition ,clot formation Tertiary hemostasis Clot retraction Cross link of fibrin clot Fibrinolysis Clotting
The Coagulation of blood is a complex process by which fluid form of blood changes to semi solid or solid form.

Bleeding E ta!asation of blood from an ruptured blood !essel to

the internal or e ternal tissue"

HEMOSTASIS AND THROMBOSIS

#ependent on $ factors%

&ascular endothelium Platelets Coagulation system

1. CLINICAL ASPECTS OF BLEEDING

'" C()*)C+( +SPECTS ,F B(EE#)*E!aluation of patients .ith bleeding is a multi/step process% Complete history #etailed physical e am (aboratory e!aluation

HISTORY

 )s there a personal or famil !is"or of bleeding after surgical procedures, dental procedures, childbirth, or trauma0 #!en the bleeding episode started0 Has the patient recei!ed me$i%a"ions that can cause or make .orse a bleeding problem0

1any drugs can contribute to bleeding2 semisynthetic penicillins cephalosporins calcium channel blocker dipyridamole thia3ides alcohol &'inine( &'ini$ine chlorproma3ine, sulfonamides )*H, rifampin methyldopa phenytoin, barbiturates, .arfarin, heparin, thrombolytic agents *S+)#s, +S+ allopurinol T)P*S)+

PH4S)C+( E5+1
'" +ssess !olume status 6correct shock if present7 8" (ook for hepatosplenomegaly $" #o a rectal e am for e!idence of -) bleeding 9" E amine oropharyn for e!idence of petechiae

HEREDIATARY TELANGECTASIAS
1outh% -um Bleed -um Hypertrophy Telangectasias +ngular stomatitis

S,BCON-,NCTI.AL HAE)ORRHAGE

PH4S)C+( E5+1

(ook for physical signs and symptoms of diseases related to %apillar fra/ili" 0 Cushing:s syndrome, 1arfan syndrome or e ogenous steroids ;senile purpura< Petechiae secondary to coughing, snee3ing, &alsal!a maneu!er, blood pressure measurement !asculitis 6;palpable purpura;7

Telangiectasias 6,sler/=eber/>endu syndrome7 6HHT7

PETECHIAE

&+SC?()T)S 6P+(P+B(E >+SH7

8" HE1+T,(,-)C #)S,>#E>S C+?S)*- B(EE#)* Platelet disorders

Coagulation factor disorders

C()*)C+( #)FFE>E*T)+T),*

P(+TE(ET #EFECT &S C,+-?(+T),* #EFECT

P(+TE(ETS #EFECTS
-enerally ha!e immediate onset of bleeding after trauma Bleeding is predominantly in skin, mucous membranes, nose, -) tract, and urinary tract Bleeding may be obser!ed as petechiae 6@$ mm7 or ecchymoses 6A$ mm

C,1P+>)S,* ,F P(+TE(ET +*# C,+-?(+4),* #)S,>#E>S

Platelet Disorders Site of bleeding Coagulation Factor Disorder

Physical Finding Family History #leeding after cuts and scratches #leeding after surgery and trauma

Skin, mucous Deep in soft tissues (joints membrane and soft and muscles) tissue Petechiae, ecchymoses Hematoma, Hemarthrosis Autosomal dominant $es &mmediate, usually mild Autosomal or !linked recessi"e %o Delayed ('!( days), often se"ere

C()*)C+( +SPECTS ,F B(EE#)*-

C,+-?(+T),* #EFECTS
;#eep; bleeding 6in the Boint spaces, muscles, and retroperitoneal spaces7 is common" ,bser!ed on e am as hematomas and hemarthroses"

Hematoma

LABORATORY E.AL,ATION OF BLEEDING

CBC and smear Platelet count Thrombocytopenia RBC and platelet morphology TTP, DIC, etc.

Coagulation pathways PTT

PT

extrinsic/common

Intrinsic/common pathways Specific factor deficiencies

(+B,>+T,>4 E&+(?+T),* ,F B(EE#)*50:50 mix Inhibitors (e.g., antibodies)

Fibrinogen assay Decreased fibrinogen Platelet function von Willebrand factor vWD Bleeding time In vivo test (non-specific) Thrombin time Qualitative/quantitative fibrinogen Platelet function analyzer (PFA) Qualitative platelet defects disorders D-dimer

Coag. factor assays

BLEEDING TIME

Fibrinolysis (DIC)

5-10% of patients hospitalized patients have a prolonged bleeding time Most of the prolonged bleeding times are due to aspirin or drug ingestion Prolonged bleeding time does not predict excess surgical blood loss Not recommended for routine testing in preoperative patients

THROMBIN TIME

Measures rate of fibrinogen conversion to fibrin Procedure:

Add thrombin with patient plasma Measure time to clot

Variables:
Source and quantity of thrombin

CAUSES OF PROLONGED THROMBIN TIME

Heparin Hypofibrinogenemia Dysfibrinogenemia Paraprotein Thrombin inhibitors (Hirudin) Thrombin antibodies

PLATELETS
APPROACH TO THE THROMBOCYTOPENIC PATIENT
History Is the patient bleeding?

2. Are there symptoms of a secondary illness? (neoplasm, infection, autoimmune disease) 3. Is there a history of medications, alcohol use, or recent transfusion? History
4. Are there risk factors for viral infection? 5.Is there a family history of thrombocytopenia? 6. Do the sites of bleeding suggest a platelet defect? Assess the number and function of platelets

CBC with peripheral smear Bleeding time Platelet aggregation study PFA

CLASSIFICATION OF PLATELET DISORDER

Quantitative disorders
Abnormal distribution Dilution effect Decreased production Increased destruction

C(+SS)F)C+T),* ,F P(+TE(ET #)S,>#E>S

Qualitative disorders
Inherited disorders (rare)

Acquired disorders
Immune Medications

Chronic renal failure Cardiopulmonary bypass Liver disease

)*HE>)TE# P(+TE(ET #)S,>#E>S 1ay/Hegglin%

Thrombocytopenia Large platelets Neutrophils Dohle bodies

.-la3mann:s thrombasthenia% Congenital deficiency or abnormality of GP IIb-IIIa

Bernard-Solier syndrome:

Congenital deficiency or abnormality of GP Ib

ACQUIRED PLATELET DISORDERS

Decreased production: Ineffective thrombopoiesis - MDS Increased destruction:

Immune Non-immune Poor aggregation INCREASED PLATELETS DESTRUCTION

ITP IS A DIAGNOSIS OF EXCLUSION !

COAG,LATION FACTOR DEFECTS

)nherited Coagulation factor bleeding disorders
C C !on=illebrand:s disease Hemophilia 6+ and B7

HE1,PH)()+
Clinical manifestations 6hemophilia + D B are indistinguishable7
C Prolonged bleeding after surgery or dental e tractions C Hemarthrosis 6most common7 C Soft tissue hematomas C ,ther sites of bleeding
?rinary tract C*S, neck 6may be life/threatening7

+CE?)>E# B(EE#)*- #)S,>#E>S%

C C C C C

&itamin F deficiency (i!er disease =arfarin o!erdose #)C )nhibitors to CF

VITAMIN K DEFICIENCY
Source of vitamin K : Green vegetables Synthesized by intestinal flora Required for synthesis Factors II, VII, IX ,X Protein C and S Causes of deficiency : Malnutrition Billiary obstruction Malabsorption Antibiotic therapy

DIC
DISSEMINATED INTRAVASCULAR COAGULATION

Sepsis Trauma
Head injury Fat embolism

Malignancy

PATHOGENESIS OF DIC
Cons'mp"ion of %oa/'la"ion fa%"ors1 presen%e of FDPs aPTT PT TT Fi2rino/en Presen%e of plasmin D3$imer In"ra4as%'lar %lo" Pla"ele"s S%!is"o% "es

HEMOSTASIS IN LIVER DISEASE LI.ER DISEASE AND HE)OSTASIS

Decreased synthesis of II, VII, IX, X, XI, and fibrinogen Dietary Vitamin K deficiency (Inadequate intake or malabsortion) Dysfibrinogenemia Enhanced fibrinolysis (Decreased alpha-2-antiplasmin) DIC Thrombocytopenia due to hypersplenism

)ANAGE)ENT OF HE)OSTATIC DEFECTS IN LI.ER DISEASE

Treatment for prolonged PT/PTT
Vitamin K 10 mg SQ x 3 days - usually ineffective

Fresh-frozen plasma infusion: 25-30% of plasma volume (1200-1500 ml) (immediate but temporary effect)

Treatment for low fibrinogen

Cryoprecipitate (1 unit/10kg body

APPROACH TO BLEEDING DISORDERS SUMMARY

Identify and correct any specific defect of hemostasis

Laboratory testing is always needed to establish the cause of bleeding Screening tests (PT,PTT, platelet count) will often allow placement into one of the broad categories Specialized testing is usually necessary to establish a specific diagnosis

Use non-transfusional drugs whenever possible RBC transfusions for surgical procedures or large blood loss

TH+*F 4,?G