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Page 1: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

HEMORRHAGIC DIATHESIS

Page 2: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY, PLATELET DISORDER (THROMBOCYTOPENIA AND THROMBOCYTOPATHY) AND VASOPATHY. EACH TYPE IS SUBDIVIDED INTO CONGENITAL AND ACQUIRED. 

Page 3: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

Petechial-ecchymosis

Hematoma

Mixed (Petechia & Hematoma)

Vasculatic

Angiomatosic

The main bleeding types

Page 4: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

THE MAIN BLEEDING SICKNESS TYPES• Hematomic (massive, deep, painful; bleeding may occur anywhere. The most

common sites of bleeding are into joints (knees, ankles, elbows), into muscles, from the gastrointestinal tract, cause of the bleeding can be intramuscular injection; characterized by early postoperative & posttraumatic bleeding)

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• hematoma

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• petechia-spotted (macula)

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MACULA-HEMATOMA

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VASCULITIC PURPURA

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ANGIOMA

Page 10: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

THE MAIN COAGULOGRAM INDEXES11 IndexIndex HypoHypo

coagulationcoagulationNormoNormo

coagulationcoagulationHyperHyper

coagulationcoagulation

Bleeding time (by Lee-Bleeding time (by Lee-White methods), minWhite methods), min

>>55 5-35-3 << 33

Platelets numberPlatelets number <<180180 180-320180-320 >>320320

Platelet adhesivenessPlatelet adhesiveness <<2323 23-4423-44 >>4545

Time of plasma Time of plasma recalcification, secrecalcification, sec

>>120120 120-60120-60 <<6060

Heparin tolerance test, Heparin tolerance test, minmin

>>1111 11-811-8 <<88

Prothrombin index, %Prothrombin index, % <<8080 80-10080-100 >>100100

U-factorU-factor <<8080 80-10080-100 >>100100

Procorventin (VII Procorventin (VII factor), %factor), %

<<8080 80-10080-100 >>100100

Fibrinogen, g/lFibrinogen, g/l <<22 2-42-4 >>44

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SCREENING TESTS FOR BLEEDING DISORDERS

TestTest Abnormality detectedAbnormality detectedBlood count and filmBlood count and film Anaemia, leukaemia, Anaemia, leukaemia,

disseminateddisseminatedintravascular coagulationintravascular coagulation

Platelet countPlatelet count ThrombocytopeniaThrombocytopeniaActivated partial thromboplastin Activated partial thromboplastin timetime

Deficiency of all coagulation Deficiency of all coagulation factorsfactorsexcept VII, especially follows VIII except VII, especially follows VIII and IX;and IX;heparinheparin

Prothrombin timeProthrombin time Deficiency of factors I, II, V, VII, Deficiency of factors I, II, V, VII, and X;and X;warfarinwarfarin

Thrombin time or fibrinogenThrombin time or fibrinogen Hypofibrinogenaemia or Hypofibrinogenaemia or dysfibrinogenaemia; heparin; dysfibrinogenaemia; heparin; fibrin degradation productsfibrin degradation products

Bleeding time Bleeding time Test of platelet-vessel wall Test of platelet-vessel wall interactioninteraction

Page 12: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

COAGULOPATHY

•I. Congenital• Deficiency of coagulation factor VIII (hemophilia A)• Deficiency of coagulation factor IX (hemophilia B)• Deficiency of coagulation factor XI (hemophilia C)• Deficiency of other coagulation factors (I, II, V, VII, IX, X and XIII) • Deficiency of XII factor, prekallikrein or kininogen, protein C and S (without excessive bleeding)• von Willebrand’s disease (angiohemophilia)

Page 13: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

COAGULOPATHY• II. Acquired• 1) Hypoprothrombinemia• • Deficiency of vitamin K due to acholia of GIT (in

cholestatic jaundice)• In overdose of indirect anticoagulant (antagonist of vitamin K)• In liver cirrhosis (due to reduced protein production)

• 2) Consumption of coagulation factors (II stage of DIC)• 3) Heparin overdose • 4) Activation of fibrinolytic system• • In administration of streptokinase etc.

• In trauma, obstetrical or surgical operations• In malignant neoplasms• In shock, sepsis, hematological malignancies, III stage of DIC

Page 14: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

PLATELET DISORDERS

•Thrombocytopathy•I. Congenital (deficiency of platelet membrane glycoprotein) – Glanzmann's Thrombasthenia•II. Acquired (normal platelet count in blood and bone marrow but its functions are decreased)•• Drugs (after intake of antiplatelet agents: aspirin, Ticlide®);• Immune, toxic, septic processes;• Hematological malignancies and anemias•Thrombocytopenia (decrease in the number of platelets)•I. Werlhof’s disease - autoimmune thrombocytopenic purpura•II. Symptomatic•• Immune (heteroimmune, isoimmune,) • Toxic (in phosphorus poisoning etc.)• Methaplastic (in hematological malignancies or myelocarcinosis)• Drug-induced (cytostatics)

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THROMBOCYTOPENIAo Thrombocytopenia (decrease in the number of

platelets) o - Idiopathic thrombocytopenic purpura (ITP) o - Thombotic thrombocytopenic purpura (TTP) o - Heparin-induced thrombocytopenia (HIT)o - Hemolytic-Uremic Syndromeo - Chronic liver disease

Page 16: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

VASOPATHY

• I. Congenital

• • Telangiectasiae (Rendu-Osler-Weber disease)• Aneurysm of fine vessels • Ehlers-Danlos syndrome, Marfan’s syndrome, retinocerebral angiomatosis (von Hippel-Lindau syndrome), encephalotrigeminal angiomatosis (Sturge-Kalisher-Weber syndrome)

• II. Acquired

• • Hemorrhagic vasculitis – Henoch-Schönlein purpura• Immune vasculitis• Systemic vasculitis• Avitaminosis of vitamin C

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THE CLOTTING MECHANISM

INTRINSIC EXTRINSIC

PROTHROMBIN THROMBIN

FIBRINOGEN

FIBRIN(II) (III)

(I)V

X

Tissue Thromboplastin

Collagen

VII

XII

XI

IXVIII

Page 18: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

COAGULATION PATHWAY• Two pathways for fibrin clot formation:

• Intrinsic• Initiated by negatively charged surface

• Extrinsic• Initiated on tissue injury

• Both pathways converge on a final common pathway

• Prothrombin Thrombin (Most critical step )• Fibrinogen Fibrin Clot

• The pathways are complex and involve many different proteins (called blood clotting factors)

Page 19: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

COAGULATION CASCADE - CONTINUED

Control of coagulation

• Antithrombins (e.g., antithrombin III)

• Proteins C and S

• Fibrinolytic cascade

• Plasminogen plasmin fibrin break down products (*FDP or FSP) – d-dimer is most important of the FDPs

*FDP / FSP – Fibrin degradation products / Fibrin split products

Page 20: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,
Page 21: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

Bleeding disorders

Vascular abnormalities

Platelet disordersClotting factorabnormalities

DIC

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CLOTTING FACTOR ABNORMALITIES

• Congenital disordersCongenital disorders• Von Willebrand disease –MC with minimal bleedingVon Willebrand disease –MC with minimal bleeding• Factor VIII Deficiency - Hemophilia A or Classic TypeFactor VIII Deficiency - Hemophilia A or Classic Type• Factor IX Deficiency – Hemophilia BFactor IX Deficiency – Hemophilia B

• Acquired disordersAcquired disorders• Vit. K deficiency Vit. K deficiency • Oral anti-coagulantsOral anti-coagulants

• Coumarin derivativesCoumarin derivatives = warfarin – inhibit Vit. K = warfarin – inhibit Vit. K factors factors

• Liver diseases ↓ synthesis of factorsLiver diseases ↓ synthesis of factors

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www.themegallery.com

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factor IX deficiency

factor VIII deficiency

factor XI deficiency

А В С

Haemophilia

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FORMS Haemophilia A - factor VIII deficiency, "classic

haemophilia" (X-linked) Haemophilia B - factor IX deficiency, "Christmas

disease" (X-linked) Haemophilia C - factor XI deficiency (Ashkenazi

Jews, autosomal recessive) The unrelated type 1 and type 2

von Willebrand disease (vWD)

Page 25: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

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Mild form

1 2

F VIII C level 1-5 %

Moderate form

3

F VIII C level less than 1 %

Severe form

F VIII C level 5-25 %

Classification (F VIII C level)

Page 26: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

CLINICAL SEVERITY OF HAEMOPHILIA A AND B

Factor value*Factor value* Bleeding tendencyBleeding tendency

Less than 0.02Less than 0.02 Severe - frequent spontaneous bleeding Severe - frequent spontaneous bleeding into joints, muscles, and internal organsinto joints, muscles, and internal organs

0.02-0.050.02-0.05 Moderate—some “spontaneous” Moderate—some “spontaneous” bleeds,bleeds,bleeding after minor traumableeding after minor trauma

More than More than 0.050.05 Mild—bleeding only after significant Mild—bleeding only after significant trauma ortrauma orsurgerysurgery

* Normal value of factors VIII and IX is 0.5-1.5* Normal value of factors VIII and IX is 0.5-1.5

Page 27: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

HEMOPHILIA AHEMOPHILIA A• MC hereditary disease with serious bleeding

• X-linked recessive• In 30% No family history (new mutations)• 15% of severe cases develop factor VIII inhibitors

• ↓ amount or activity of factor VIII• factor VIII = cofactor for activation of factor X in the

coagulation cascade• Symptoms usually – hemoarthrosis, bruising,

hemorrhage after trauma or surgery

Page 28: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

SIGNS & SYMPTOMS •

Symptoms of hemophilia are usually first noticed during infancy or childhood. However, some people with milder forms of hemophilia may not develop symptoms until later on.

The following are signs of hemophilia that may be noticed shortly after birth: Bleeding into the muscle, resulting in a deep bruise after receiving a routine vitamin K shot.

Prolonged bleeding after a male child is circumcised. •

Other symptoms of hemophilia include: Bleeding into a joint or muscle that causes pain and swelling. Abnormal bleeding after an injury. Easy bruising. Frequent nosebleeds. Blood in the urine (hematuria).

• The most common bleeding problem a person with severe hemophilia has is bleeding into a joint (hemarthrosis), often without an injury.

Page 29: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,
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Arhtropathy

Hematomic bleeding sickness types

Diagnostic criteria

Hemophilia

Page 31: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,
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Page 33: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,
Page 34: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

BIOCHEMICAL ASPECTS:

• Factor VIII circulates in the plasma as a complex of factor VIII and von Willebrand factor. The molecular weight of human factor VIII has been estimated to be 285,000. Hemophelia A in which factor VIII (antihemophelic factor) is either absent or dysfunctional is transmitted by X chromosomal inheritance. Hemophelia A is at least four times more common than hemophelia B.

Page 35: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,
Page 36: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

DIAGNOSTIC CRITERIA

• Family_history_of_coagulation_disorders: positive APTT:abnormal

• Mixing_APTT:corrected Factor_VIII:C_activity:abnormal

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Condition Prothrombin time

Partial thromboplastin time

Bleeding time Platelet count

Vitamin K deficiency or warfarin

prolongednormal or mildly prolonged

unaffected unaffected

Disseminated intravascular coagulation

prolonged prolonged prolonged decreased

von Willebrand disease

unaffected prolonged prolonged unaffected

Hemophilia unaffected prolonged unaffected unaffectedAspirin unaffected unaffected prolonged unaffectedThrombocytopenia

unaffected unaffected prolonged decreased

Uremia unaffected unaffected prolonged unaffectedGlanzmann's thrombasthenia

unaffected unaffected prolonged unaffected

Bernard-Soulier syndrome

unaffected unaffected prolongeddecreased or unaffected

Page 38: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

TREATMENT

• In mild bleeding: 1-desamino-8-D-arginine vasopressin (DDAVP). The level of factor VIII must be maintained at least 30%.

• In non-life-threatening bleeding or pre-op: factor VIII concentrates. The minimal hemostatic level of factor VIII:C in this case is 50%.

• Central nervous system hemorrhage and severe bleeding: factor VIII concentrates. The level of factor VIII:C must be maintained at 80% - 100%.

• Each unit of factor VIII concentrates will raise the level of factor VIII by 2%/kg of body weight.

• Adjunctive therapy in dental surgery for mild and moderate hemophelia A: epsilon-aminocaproic acid (EACA).

• Avoidance of aspirin-containing compounds. • For monitoring therapy, factor VIII assay is the test of choice. • Dosage: the (activity ) units of factor VIII required can be calculated

from: 40*BW*(desired factor level-actual factor level)/100 • where BW is body weight in kg

Page 39: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

TREATMENT

• The dose of factor VIII concentrate is calculated assuming that one unit of factor VIII is the amount present in 1 mL of plasma. Plasma volume is 40 mL/kg, and the volume of distribution of factor VIII:C is 1.5 times the plasma volume. Thus, to raise the level 100%, the dose should be 40 x 1.5 = 60 units/kg, or approximately 4000 units for a 70-kg individual. To raise the levels to 25% would require 1000 units. The half-life of factor VIII:C is approximately 12 hours. Thus, during major surgery, to achieve an initial level of 100% and maintain it continuously at greater than 50%, a dose of 60 units/kg (approximately 4000 units) initially followed by 30 units/kg (approximately 2000 units) every 12 hours should be adequate. During surgery, initially verify that these doses give the anticipated factor VIII levels. If factor VIII levels fail to rise as expected, an inhibitor should be suspected.

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HEMOPHILIA BHEMOPHILIA B

• DEFICIENCY OF FACTOR IX• Factor IX deficiencyFactor IX deficiency• X-linked recessiveX-linked recessive• Much less commonMuch less common• Clinically= Clinically= indistinguishableindistinguishable from Hemophilia A from Hemophilia A

with with Similar lab findingsSimilar lab findings• Diagnosis by factor IX levelsDiagnosis by factor IX levels• Treat with recombinant IXTreat with recombinant IX

Page 41: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

DIAGNOSTIC CRITERIA

• Family_history_of_coagulation_disorders:positive

• Mixing_APTT:corrected

• Factor_IX_assay:abnormal

• APTT:abnormal

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TREATMENT

• For patients with mild form of factor IX deficiency with non-life-threatening bleeding, the treatment of choice is FFP. For the severe form of hemophelia B or in life- threatening situation, prothrombin complex concentrates are the treatment of choice.

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TREATMENT

• Target levels of factor IX for therapy: Severe hemorrhage: 20% - 50% for 3-5 days, then 10% - 20% for the next 10 days.

• Minor hemorrhage: 20% for 7 days.

• Surgery: 50% - 70% for 2 days, then 30% - 40% for 3 days, then 20% for 7 days.

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TREATMENT

• Dosage: the (activity) units of factor IX required can be calculated from: 80*BW*(desired factor level-actual factor level)/100

• where BW is body weight in kg

• Note that in-vivo recovery of factor IX is about 50%.

Page 45: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

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15-20 UN/kg

1 2

Moderate

35-40 UN/kg

3

Severe.

70 UN/kg

Mild

Hemophilia A Treatment (cryoprecipitate)

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VON WILLEBRAND'S DISEASE

Essentials of Diagnosis

• Family history with autosomal dominant pattern of inheritance.

• Prolonged bleeding time, either at baseline or after challenge with aspirin.

• Reduced levels of factor VIII antigen or ristocetin cofactor.

• Reduced levels of factor VIII coagulant activity in some patients.

Symptoms and Signs

• von Willebrand's disease is a common disorder affecting both men and women. Most cases are mild. Most bleeding is mucosal (epistaxis, gingival bleeding, menorrhagia), but gastrointestinal bleeding may occur. In most cases, incisional bleeding occurs after surgery or dental extractions. von Willebrand's disease is rarely as severe as hemophilia, and spontaneous hemarthroses do not occur (except in the rare type III). The bleeding tendency is exacerbated by aspirin. Characteristically, bleeding decreases during pregnancy or estrogen use.

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Page 48: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

THE MAIN BLEEDING SICKNESS TYPES• Mixed (Petechial & Hematomic) (combined

features of both types, but there are some difference: in contrast to hematomic - bleeding are into joints very rare, mostly it is located in subcutaneous, retroperitoneal, mesenteric, subserous intestinal layer or into internal organ);in contrast to petechial-ecchymosic bleeding - hemorrhagic syndrome characterized by large bruise)

Page 49: HEMORRHAGIC DIATHESIS. HEMORRHAGIC DIATHESIS IS A DISEASE, CHARACTERIZED BY EXCESSIVE BLEEDING. ACCORDING TO PATHOGENESIS, IT IS CLASSIFIED INTO COAGULOPATHY,

TREATMENT• The bleeding disorder is characteristically mild, and no treatment is

routinely given other than avoidance of aspirin. However, patients often need to be prepared for surgical or dental procedures. The bleeding time is probably the best indicator of the likelihood of bleeding, and prophylactic therapy may be reasonably withheld if the procedure is minor and the bleeding time is normal.

• Desmopressin acetate (DDAVP) is useful for mild type I von Willebrand's disease and should be considered first. The dose is 0.3 mcg/kg, after which vWF levels usually rise two- to threefold in 30–90 minutes. It can also be given as a nasal spray; levels peak 2 hours after use.

• The antifibrinolytic agent aminocaproic acid (EACA) is useful as adjunctive therapy during dental procedures.

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PLATELET HEMOSTATIC ACTIVITY

• 1. Pl stimulate vasoconstriction of injured vessels

• 2. Pl form hemostatic plug (platelet adhesion) + platelet aggregation to seal small vessel wall

• 3. Pl play role in fibrin clot formation

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Bleeding disorders

Vascular abnormalities

***Platelet disorders

Clotting factorabnormalities

DIC

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Bleeding disorders

Platelet disorders

↓production ↑destruction

SequestrationHypersplenism

Primary/IdiopathicITP

Acute/Chronic

SecondaryDrugs, HIV

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THROMBOCYTOPENIA• Thrombocytopenia (or -paenia, or thrombopenia in short) is the

presence of relatively few platelets in blood.

• Generally speaking a normal platelet count ranges from 180,000 and 320,000 per mm3.

• Signs and symptoms

• Often, low platelet levels do not lead to clinical problems; rather, they are picked up on a routine full blood count. Occasionally, there may be bruising, nosebleeds and/or bleeding gums.

• It is vital that a full medical history is elicited, to ensure the low platelet count is not due to a secondary process. It is also important to ensure that the other blood cell types red blood cells, and white blood cells, are not also suppressed.

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THROMBOCYTOPENIA

Petechial-ecchymosic

Diagnostic criteria

1. Deacrease of platelets

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PLATELET DISORDERSPLATELET DISORDERS

• Thrombocytopenia = Reduced platelet number

• Causes

• Decreased production of platelets

• vitamin B12 or folic acid deficiency

• Decreased platelet survival

• Immunologic or Nonimmunologic etiology

• Sequestration- Hypersplenism

• ameliorated by splenectomy

• Dilutional

• Massive transfusions

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IMMUNE THROMBOCYTOPENIC PURPURA (ITP) • Cause

• Antiplatelet antibodies • Antigen - platelet membrane glycoprotein complexes

IIb-IIIa and Ib-IX• Morphology

• Peripheral Blood• thrombocytopenia, abnormally large platelets

(megathrombocytes or Giant platelets),• Marrow

• Normal or Increased magakaryocyte #• Diagnosis - by exclusion

• Bleeding time - prolonged, but PT & PTT - normal

↓ Marrow magakaryocyte # - your Diagnosis of ITP is ?????

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NECESSARY EVALUATION

• • History: Isolated bleeding symptoms consistent with

thrombocytopenia without constitutional symptoms

(e.g. significant weight loss, bone pain, night sweats).

• • Physical examination: Bleeding symptoms in the absence of hepatosplenomegaly, lymphadenopathy, or stigmata of congenital conditions.

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NECESSARY EVALUATION

• • Complete blood count: Isolated thrombocytopenia (platelet count <100 x 109/L). Anemia only if due to significant bleeding—otherwise normal red cell indices, white blood cell count and differential.

• • Peripheral blood smear: Identified platelets should be normal to large in size. Red and white blood cell morphology should be normal.

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BONE MARROW EVALUATION• • Bone marrow examination is unnecessary in patients with the

typical features of ITP outlined above, irrespective of the age of the patient.

• • Bone marrow examination is felt to be unnecessary in children with typical ITP prior to initiation of treatment with corticosteroids, prior to splenectomy, or in patients who fail intravenous immunoglobulin (IVIg) therapy.

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BONE MARROW EVALUATION• • The presence of abnormalities in the history, physical

examination, or the complete blood count and peripheral blood smear should be further investigated, e.g. with a bone marrow examination or other appropriate investigations, before the diagnosis of ITP is made.

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ADDITIONAL EVALUATIONS

• • All adult patients with newly diagnosed ITP should undergo testing for HIV and HCV.

• • There is insufficient evidence to support the routine use of anti-platelet, antiphospholipid, and anti-nuclear antibodies, thrombopoietin levels, or platelet parameters obtained on automated analyzers in the evaluation of patients with suspected ITP.

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DIAGNOSTIC CRITERIA:

• Plt_count:abnormal (low)

• Peripheral blood smear:no increase in schistocytes

• Bone_marrow:megakaryocytosis

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THE MAIN BLEEDING SICKNESS TYPES• Petechia-ecchymosis (is usually localized to superficial sites such

as the skin and mucous membranes, wich often combined with menorrhagia, nose bleeding, gumms bleeding; rare – with gastrointestinal bleeding or brain hemorrhage; it is small, painless, provoked by simple action like skin cleaning, measure of blood pressure etc; pinch test is positive)

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ITP

FeatureFeature AcuteAcute ChronicChronic

Age / SexAge / Sex ChildrenChildren Adult/FemaleAdult/Female

OnsetOnset AbruptAbrupt GradualGradual

Predisposing Predisposing FactorsFactors

Viral infection/ Viral infection/ vaccinevaccine

--

DurationDuration <2 months<2 months >6mnoths>6mnoths

PathogenesisPathogenesis -- IgG against Platelet IgG against Platelet GPGP

Peripheral Peripheral smearsmear

Thrombocytopenia & Thrombocytopenia & Giant PLTSGiant PLTS

SameSame

Bone marrowBone marrow Normal or Normal or ↑Megakaryocytes↑Megakaryocytes

SameSame

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ITP

FeatureFeature AcuteAcute ChronicChronic

TestsTests Prolonged BT Prolonged BT & Normal PT & & Normal PT & PTTPTT

SameSame

Complication Complication (most (most dangerous)dangerous)

Intracranial Intracranial bleedbleed

SameSame

Clinical courseClinical course Spontaneous Spontaneous remissionremission

NoNo

TreatmentTreatment PLT. PLT. TransfusionTransfusion SplenectomySplenectomy

If <20,000If <20,000

NoNoIf <50,000If <50,000

Yes (refractory Yes (refractory cases)cases)

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ConditionProthrombin time

Partial thromboplastin time

Bleeding time Platelet count

Vitamin K deficiency or warfarin

prolongednormal or mildly prolonged

unaffected unaffected

Disseminated intravascular coagulation

prolonged prolonged prolonged decreased

von Willebrand disease unaffected prolonged prolonged unaffected

Hemophilia unaffected prolonged unaffected unaffected

Aspirin unaffected unaffected prolonged unaffected

Thrombocytopenia

unaffected unaffected prolonged decreased

Uremia unaffected unaffected prolonged unaffectedGlanzmann's thrombasthenia

unaffected unaffected prolonged unaffected

Bernard-Soulier syndrome

unaffected unaffected prolongeddecreased or unaffected

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MANAGEMENTOF ITP• The goal of all treatment strategies for ITP is to achieve a platelet

count that is associated with adequate hemostasis, rather than a normal platelet count. The decision to treat should involve a discussion with the patient and consideration of the severity of bleeding, anticipated surgical procedures, medication side effects, and health-related quality of life.

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INITIAL MANAGEMENT OF ITP• Assessment of Disease Status:

• • What bleeding is the patient experiencing?

• • Determine the timing, location, and severity of

• bleeding symptoms.

• • Does this patient have any additional risk factors for bleeding such as use of antithrombotic agents or high-risk occupation?

• • Is a surgical procedure anticipated?

• • Is this patient likely to comply with recommended treatments?

• • Is the bleeding experienced by this patient interfering with his or her daily activities or causing significant anxiety?

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GENERAL CONSIDERATIONS FOR INITIAL MANAGEMENT

• • The majority of patients with no bleeding or mild bleeding (defined here as skin manifestations only, such as petechiae and bruising) can be treated with observation alone regardless of platelet count.

• • First-line treatment includes observation, corticosteroids, IVIg, or anti-D immunoglobulin (anti-D).

• • Anti-D should be used with caution given recent FDA warnings of severe hemolysis. It is therefore not advised in patients with bleeding causing a decline in hemoglobin, or those with evidence of autoimmune hemolysis.

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DRUG INDUCED THROMBOCYTOPENIAHEPARIN INDUCED THROMBOCYTOPENIA (HIT)

• Seen in 3-5% of patients treated with unfractionated heparin

thrombocytopenic after 1-2 weeks of Rx

• Caused by IgG antibodies against platelet factor 4/heparin complexes on platelet surfaces

• Exacerbates thrombosis, both arterial and venous (in setting of severe thrombocytopenia)

• Antibody binding results in platelet activation and aggregation.

• Rx - cessation of heparin

Other drugs???

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PLATELET FUNCTIONAL DISORDERSPLATELET FUNCTIONAL DISORDERS

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Bleeding disorders

Vascular abnormalities

Platelet disordersClotting factorabnormalities

DIC

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VASCULAR ABNORMALITIESVASCULAR ABNORMALITIES• Causes

• Infections• Meningococcemia, Rickettsioses , Infective endocarditis

• Drug reactions

• Hereditary hemorrhagic telangiectasia• Autosomal dominant

• Cushing syndrome

• Henoch - Schönlein Purpura • systemic hypersensitivity disease of unknown cause

• polyarthralgia, and acute Glomerulonephritis

• Palpable purpuric rash, colicky abdominal pain

• Scurvy and the Ehlers-Danlos syndrome

• Amyloid infiltration of blood vessels

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THE MAIN BLEEDING SICKNESS TYPES

• Vasculatic (hemorrhage due to inflammatory changes of small vessels, the main cause are immune disorders

or infectious agent)

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THE MAIN BLEEDING SICKNESS TYPES• Angiomatosic (hemorrhage due to vascular dysplasia,

teleangiectasia; the main clinical criteria is relapsing bleeding without hemorrhage in skin, subcutaneous and other tissue; nose bleeding are most often, dangerous and massive)

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Bleeding disorders

Vascular abnormalities

Platelet disordersClotting factorabnormalities

DIC

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Thank you for attention!