APPROACH TO A BLEEDING PATIENT

Dr. CENGİZ CANPOLATDr. CENGİZ CANPOLAT

How do the patients presentHow do the patients present

1-referral from a family physician or 1-referral from a family physician or pediatricianpediatrician

2-detection of a bleding problem in a 2-detection of a bleding problem in a family member and bringing the family member and bringing the child over for investigationchild over for investigation

3-detection of an abnormal physical 3-detection of an abnormal physical or laboratory finding during routine or laboratory finding during routine clinic visitclinic visit

How do the patients presentHow do the patients present

4-detection of an abnormality in 4-detection of an abnormality in preoperative lab tests.preoperative lab tests.

5-unexplained bleeding during or 5-unexplained bleeding during or after surgery or following a after surgery or following a trauma trauma

6-presentation to ER with an 6-presentation to ER with an active bleedingactive bleeding

How to approachHow to approach

Detailed history Detailed history

Systemic PE Systemic PE

Lab testsLab tests

Helps to determine whether the Helps to determine whether the condition is hereditary or acquiredcondition is hereditary or acquired

Helps to predict where the Helps to predict where the abnormality lies inabnormality lies in

-vessel wall?-vessel wall?

-platelets?-platelets?

-clotting factors?-clotting factors?

History History

HistoryHistory

Specific questions should be asked:Specific questions should be asked:

-is there excessive bleeding during -is there excessive bleeding during dental procedures, circumcision, or dental procedures, circumcision, or minor cuts?minor cuts?

-is there a history of spontaneous -is there a history of spontaneous echymosis, intramuscular or echymosis, intramuscular or intraarticular bleeding?intraarticular bleeding?

-is there a history of blood or blood -is there a history of blood or blood pruduct transfusion? pruduct transfusion?

Age when the first symptoms Age when the first symptoms beginbegin

Newborn: Newborn: cephal hematoma cephal hematoma increasing in size may suggest increasing in size may suggest severe hemophilia or hemorrhagic severe hemophilia or hemorrhagic disease of the newborn disease of the newborn

Umblical bleeding may also occur in Umblical bleeding may also occur in bothboth

Bleeding occurs in the first weeks of Bleeding occurs in the first weeks of life in one third of the hemophilia life in one third of the hemophilia patients and in less then 10% of the patients and in less then 10% of the other hereditery clotting diseasesother hereditery clotting diseases

Bleeding in the first few months of Bleeding in the first few months of lifelife

Hemorrhagic disease of the Hemorrhagic disease of the newbornnewborn

Intrauterine infections (TORCH)Intrauterine infections (TORCH)

Maternal ITP, SLE Maternal ITP, SLE

Maternal drug exposure Maternal drug exposure

TAR syndromeTAR syndrome

Congenital amegakaryocytic Congenital amegakaryocytic thrombocytopeniathrombocytopenia

Age Age

Hemophilic bleeding starts at age 1-Hemophilic bleeding starts at age 1-2 2

ITP is usually seen between 2-4 ITP is usually seen between 2-4 years of age years of age

Henoch-Schönlein purpura peaks at Henoch-Schönlein purpura peaks at age 4-7 age 4-7

Bleeding type and Bleeding type and disseminationdissemination

Petechia, purpura, echymosisPetechia, purpura, echymosis

• the size, number and dissemination as the size, number and dissemination as well as whether they occured well as whether they occured spontaneously or after a trauma should spontaneously or after a trauma should be taken into accountbe taken into account

• occurrence in areas remote from occurrence in areas remote from trauma such as trunk or back should trauma such as trunk or back should suggest bleeding tendencysuggest bleeding tendency

PetechiaPetechia• on legs where the venous pressure is highon legs where the venous pressure is high • in the head and neck area in the in the head and neck area in the

crying child crying child • Pressure areas from the belt or socks Pressure areas from the belt or socks • Areas where the child scratches Areas where the child scratches • On the mucous membranes (wet On the mucous membranes (wet

petechia)petechia)

bleeding type clotting factor def. Platelet and vascular Petechia rare typical

Deep hematoma typical rare

Ecchymosis freq. generally big ,single typical, gen. small multiple

Hemarthrosis typical rare

prolonged bleed. Freq. rarebleed. superf. cut Minimal Persistant, freq. heavysex 80-90%male freq. in females

family history + rare except vWD and HHT

Nutrition and medication Nutrition and medication historyhistory

Especially aspirin and NSAID that Especially aspirin and NSAID that impair platelet fx impair platelet fx

Many other drugs can also cause Many other drugs can also cause thrombocytopenia thrombocytopenia

Prolonged use of wide spectrum Prolonged use of wide spectrum antibiotics may result in vit K antibiotics may result in vit K deficiency deficiency

Nutrition and medication Nutrition and medication historyhistory

Pts with malnutrition or Pts with malnutrition or malabsorbtion may have alterations malabsorbtion may have alterations in the levels of the clotting factors in the levels of the clotting factors dependent on vit K dependent on vit K

Bleeding on the skin may be Bleeding on the skin may be secondary to vit C deficiencysecondary to vit C deficiency

Bleeding tendency may take place in Bleeding tendency may take place in the presence of liver or kidney the presence of liver or kidney disease. disease.

Procedures and surgeryProcedures and surgery

Absence of significant bleeding Absence of significant bleeding during dental extraction, during dental extraction, circumcision, surgery and major circumcision, surgery and major injuries may! rule out hemostatic injuries may! rule out hemostatic problemsproblems

Clinical presentationClinical presentation

Echymosis on the skin as well as Echymosis on the skin as well as painful swelling in the joints in a painful swelling in the joints in a toddler suggest hemophilia toddler suggest hemophilia

Echymosis and petechia following a Echymosis and petechia following a viral infection without active viral infection without active bleeding in an otherwise well child bleeding in an otherwise well child suggests ITPsuggests ITP

Repetitive excessive menstrual bleeding Repetitive excessive menstrual bleeding and bilateral epistaxis in a 16 yo female and bilateral epistaxis in a 16 yo female may be due to vWDmay be due to vWD

A child presenting to the ER with fever A child presenting to the ER with fever nuchal rigidity, shock and mucocutaneous nuchal rigidity, shock and mucocutaneous purpura should alert the physician for DIC purpura should alert the physician for DIC secondary to meningococcemia or gram secondary to meningococcemia or gram (-) sepsis.(-) sepsis.

Clinical presentationClinical presentation

Clinical presentationClinical presentation

Female pt in her second decade with Female pt in her second decade with insidious recurrent petechia and insidious recurrent petechia and echymosis and a history of autoimmune echymosis and a history of autoimmune disease in the family suggest chronic ITP disease in the family suggest chronic ITP

Malignant disease should also be kept in Malignant disease should also be kept in mind in children presenting with bleeding. mind in children presenting with bleeding. Bone or joint pain, weight loss, Bone or joint pain, weight loss, hepatosplenomegaly, lymphadenopathy, hepatosplenomegaly, lymphadenopathy, abdominal distension or palpable masses abdominal distension or palpable masses should be carefully evaluated should be carefully evaluated

Menstural bleedingMenstural bleeding

Prolonged and excessive Prolonged and excessive bleeding is typical for platelet bleeding is typical for platelet disorders or vWDdisorders or vWD

Use of oral contraseptives, Use of oral contraseptives, being anemic, using iron being anemic, using iron medication for iron deficiency medication for iron deficiency are clues to suspect prolonged are clues to suspect prolonged mensesmenses

HemarthrosisHemarthrosis

Typical bleeding for hemophilia Typical bleeding for hemophilia Most commonly affected joints are Most commonly affected joints are knee, elbow and ankleknee, elbow and anklePain, swelling and restriction in Pain, swelling and restriction in motion occur. Skin is tense and warmmotion occur. Skin is tense and warm Depending on the severity of the Depending on the severity of the disease, it’s usually seen around age disease, it’s usually seen around age 1-2 1-2 Recurrent bleeding in a single joint Recurrent bleeding in a single joint may lead to target joint and chronic may lead to target joint and chronic synovitissynovitis

Other types of bleedingOther types of bleeding

Epistaxis and gingival bleeding Epistaxis and gingival bleeding are frequently seen in platelet are frequently seen in platelet disorders and vWD disorders and vWD

Prolonged wound healing, Prolonged wound healing, formation of abnormal scar formation of abnormal scar tissue, late falling of the umblical tissue, late falling of the umblical cord may be secondary to cord may be secondary to afibrinogenemia, afibrinogenemia, dysfibrinogenemia or F XIII dysfibrinogenemia or F XIII deficiencydeficiency

Rare bleeding typesRare bleeding types

melena melena

hematemesishematemesis

hemoptisia hemoptisia

hematuria, hematuria,

retinal bleedingretinal bleeding

retroperitonal or iliopsoas muscle retroperitonal or iliopsoas muscle bleeding bleeding

CNS bleedingCNS bleeding

Family historyFamily historyConsanguinity should be asked in terms of Consanguinity should be asked in terms of autosomal recessively inherited diseases autosomal recessively inherited diseases

The presence of hemophilia, vWD, other The presence of hemophilia, vWD, other factor deficiencies, hereditary platelet factor deficiencies, hereditary platelet functional disorders, TAR syndrom, functional disorders, TAR syndrom, Wiskott-Aldrich syndrome should be Wiskott-Aldrich syndrome should be questioned questioned

The possibility of spontaneous mutations The possibility of spontaneous mutations in 30-40% of hemophilia patients should in 30-40% of hemophilia patients should be kept in mindbe kept in mind

LaboratoryLaboratory

CBCCBC, especially platelet number , especially platelet number

PPeripheral blood smeareripheral blood smear

PProthrombine time (PT) rothrombine time (PT)

AActivated partial ctivated partial thromboplastine time (aPTT)thromboplastine time (aPTT)

Platelets Platelets

Size of the platelets (MPV) is also Size of the platelets (MPV) is also important important

Normally MPV 7-11 fL, it is >10 Normally MPV 7-11 fL, it is >10 fL in ITP, <6 fL in WASfL in ITP, <6 fL in WAS

Platelets Platelets

Macroplatelets are seen in Bernard-Macroplatelets are seen in Bernard-Soulier syndrome, May-Hegglin Soulier syndrome, May-Hegglin anomaly and, Gray platelet anomaly and, Gray platelet syndrome…syndrome…

MMicroplatelets are seen in TAR icroplatelets are seen in TAR syndrome, iron deficiency anemia syndrome, iron deficiency anemia and storage pool disease and storage pool disease

A patient with purpura but normal A patient with purpura but normal platelet countplatelet count

VVascular reasonsascular reasons

(hereditary hemorrhagic (hereditary hemorrhagic telengiectasia, Ehlers-Danlos telengiectasia, Ehlers-Danlos syndrome, Henoch-Schönlein syndrome, Henoch-Schönlein purpura, purpura fulminans, SLE ) purpura, purpura fulminans, SLE )

oror

Platelet functional disordersPlatelet functional disorders

Bleeding timeBleeding time

Measures the vascular and Measures the vascular and platelet phase of hemostasisplatelet phase of hemostasisDifficult to interpret because of Difficult to interpret because of the interperformer variabilitythe interperformer variability Not considered reliable when Not considered reliable when evaluating a patient with evaluating a patient with bleeding tendency. Normal result bleeding tendency. Normal result does not rule out an abnormality does not rule out an abnormality and it can not be used as a and it can not be used as a screening testscreening test

A patient with normal platelet A patient with normal platelet number but prolonged bleeding number but prolonged bleeding

timetime

vWFag, Ristocetin cofactor vWFag, Ristocetin cofactor activity, aPTT, FVIII activity activity, aPTT, FVIII activity should be measured should be measured

Any abnormality in these tests Any abnormality in these tests will suggest the presence of the will suggest the presence of the most common congenital most common congenital bleeding disorder, vWDbleeding disorder, vWD

Not vWD but still prolonged Not vWD but still prolonged bleeding timebleeding time

PPlatelet aggregation tests latelet aggregation tests (with ADP, epinephrin, collagen, (with ADP, epinephrin, collagen, ristocetin) ristocetin)

This test will tell if there are any This test will tell if there are any adhesion, aggregation or release adhesion, aggregation or release defects in the platelets defects in the platelets

Platelet functional abnormalitiesPlatelet functional abnormalities

In Glanzmann thrombasthenia In Glanzmann thrombasthenia absence of aggregation with ADP, absence of aggregation with ADP, collagen and epinephrin is collagen and epinephrin is characteristiccharacteristic

Abnormal response to ristocetin is Abnormal response to ristocetin is seen in vWD and Bernard-Soulier seen in vWD and Bernard-Soulier syndrome syndrome

Recently, platelet functions are Recently, platelet functions are measured with a device called PFA-measured with a device called PFA-100 (Platelet Function Analyzer) and 100 (Platelet Function Analyzer) and more accurate results are obtainedmore accurate results are obtained

Plasma phase of coagulationPlasma phase of coagulation

Tests that measure the plasma Tests that measure the plasma phase of hemostasisphase of hemostasis

aPTT , PT, TT (thrombin time) and aPTT , PT, TT (thrombin time) and fibrinogen fibrinogen

aPTT measures intrinsic and aPTT measures intrinsic and common pathway, PT measures common pathway, PT measures exstrinsic and common pathwayexstrinsic and common pathway

normal value of aPTT is 20-35 sec. normal value of aPTT is 20-35 sec. It may be as long as 50-85 sec in It may be as long as 50-85 sec in newborns and premature babies newborns and premature babies

aPTT prolonged PT normalaPTT prolonged PT normal

In order to differentiate whether the In order to differentiate whether the prolongation is due to factor deficiency prolongation is due to factor deficiency or the presence of an inhibitor, or the presence of an inhibitor, patient’s plasma is mixed 1:1 with patient’s plasma is mixed 1:1 with normal plasma and aPTT is repeated normal plasma and aPTT is repeated (mixing test)(mixing test)aPTT returns to normal in clotting aPTT returns to normal in clotting factor deficiencyfactor deficiency it remains prolonged in the presence it remains prolonged in the presence of heparin, lupus anticoagulant (LA) or of heparin, lupus anticoagulant (LA) or antibodies directed against the clotting antibodies directed against the clotting factors (anti phospholipid antibodies)factors (anti phospholipid antibodies)

aPTT prolonged PT normalaPTT prolonged PT normal

Deficiencies of Factors VIII, IX, XI, XII, Deficiencies of Factors VIII, IX, XI, XII, Precallicrein (Fletcher trait), HMWK Precallicrein (Fletcher trait), HMWK (Fitzgerald trait), presence of LA or (Fitzgerald trait), presence of LA or heparin effect heparin effect Only deficiencies of FVIII, IX and XI can Only deficiencies of FVIII, IX and XI can cause clinical bleedingcause clinical bleeding aPTT stays normal until the F level aPTT stays normal until the F level drops below 30% and even until 15-drops below 30% and even until 15-18%18%

aPTT prolonged PT normalaPTT prolonged PT normal

The diagnosis of hemophilia A and B The diagnosis of hemophilia A and B are established by measuring the are established by measuring the FVIII and FIX levelsFVIII and FIX levels

It is classified according to the factor It is classified according to the factor level as severe (<1%), moderate (1-level as severe (<1%), moderate (1-5%), and mild (5-25%) hemophilia 5%), and mild (5-25%) hemophilia

Most of the cases are hemophilia A Most of the cases are hemophilia A (80-85%) and severe type (50-70%).(80-85%) and severe type (50-70%).

PT prolonged aPTT normalPT prolonged aPTT normal

Typical for F VII deficiencyTypical for F VII deficiency

PT is prolonged if the levels of one or PT is prolonged if the levels of one or more than one of the Factors II, V, VII more than one of the Factors II, V, VII and X are <40%and X are <40%

If fibrinogen level is <100mg/dl, PT If fibrinogen level is <100mg/dl, PT is prolongedis prolonged

Normal value for PT is 11-12,5 sec in Normal value for PT is 11-12,5 sec in children and adults, 12,8-14,4 sec in children and adults, 12,8-14,4 sec in term infants and 14,6-18,4 sec. in term infants and 14,6-18,4 sec. in premature babiespremature babies

PTPTProlonged values in infants normalize Prolonged values in infants normalize within 2-6 monthswithin 2-6 months

INR (International Normalized Ratio)INR (International Normalized Ratio) is calculated to prevent the is calculated to prevent the differences between laboratories due differences between laboratories due to the use of different to the use of different thromboplastine for the thromboplastine for the measurement of PTmeasurement of PT

Both aPTT and PT are prolongedBoth aPTT and PT are prolonged

In this case TT is measured. If it is normal; In this case TT is measured. If it is normal; liver disease, vit K deficiency, coumadin liver disease, vit K deficiency, coumadin effect or presence of anticoagulants should effect or presence of anticoagulants should be considered be considered

If TT is prolonged, afibrinogenemia, If TT is prolonged, afibrinogenemia, dysfibrinogenemia and DIC are the possible dysfibrinogenemia and DIC are the possible diagnosisdiagnosis

Faktör X, V, prothrombin ve fibrinogen Faktör X, V, prothrombin ve fibrinogen deficiencies or inhibitors against these deficiencies or inhibitors against these factors should be investigatedfactors should be investigated

It may sometimes be seen in patients with It may sometimes be seen in patients with high Htc (congenital syanotic heart disease)high Htc (congenital syanotic heart disease)

Conditions in which all tests are Conditions in which all tests are

normalnormal mild vWD, mild hemophilia, FXI ve mild vWD, mild hemophilia, FXI ve FXIII deficiency, some forms of FXIII deficiency, some forms of dysfibrinogenemiadysfibrinogenemia

HHereditery hemorrhagic ereditery hemorrhagic telengiectasia, alergic ve vascular telengiectasia, alergic ve vascular purpuraspurpuras

2-plasmin inhibitor deficiency, 2-plasmin inhibitor deficiency, elevation of the levels of elevation of the levels of plasminogen activatorplasminogen activator

Kanama diatezi

Öykü-FM

Trombosit sayısıNormal

Düşük Trombositopeni nedenleriNormal PT,APTT,TT

Akut hastalık Anormal

Evet Hayır Kanama öyküsü

Var

Yok FVIII,vWagRicof

Çocuk istismarıNormal Anormal

MeningokokPurpura fulminans Plt. Disfonk. vWHVaricella Variant vWH Hafif HA veya taşıyıcıPnomokok Hafif hemofiliHafif DIC Hemofili taşıyıcısıPro C.S, ATIII eks. FXIII ve hafif FXI eks.

PT, APTT, TT

Anormal

Hasta ile normal plazma karıştırılır

Düzelir Düzelmez

Uzun APTT Uzun PT Uzun TT TT APTT

Kanama öyküsü Sadece PT uzun 1:1 karışımla RT

Yok Var düzelir

FVII eks.

FVIII,vWag FVIII, FIX, XI Oral antikoag Hipo-disfib

vWRicof vWag,vWRicof rinojenemi

PT+APTT uzun

Normal karışımla Lupus AK

Oral antikoag düzelmez Heparin

FIX, XI, XII vWH Kc hast Reptilaz N

HA veya HB Vit K eks Heparin

FXI, XII eks Şiddetli FXI eks. Hafif DIC Rep T uzun

Hafif HB veya taşıyıcı FII,V,X eks Fibrin YÜ

Prekallikrein veya

HMWK eks.

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