Bleeding disorders

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Bleeding disorders

• K. Bernášková

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The Hemostatic System
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Hemostasis (clot formation)

• Primary hemostasis
• function of blood vessels and platelets
• Vasoconstriction
• Platelet plug formation
• Secondary hemostasis
• function of coagulation factors
• Definitive (insoluble) plug formation

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Primary hemostasis
1. Vasoconstriction
sympaticus
axo-axonal reflex
TXA2
serotonin
2. Primary clot formation
(a) Platelet adhesion
(b) P. aggregation
(c) P. activation
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Secondary hemostasis

• Coagulation factors

No Clotting factor Liver Vit K.
I. Fibrinogen
II. Prothrombin
III. Tissue factor (thromboplastin)
IV. Calcium
V. Proaccelerin
VII. Proconvertin
VIII. AHF A, vW
IX. Christmas factor (AHF B)
X. Stuart Prower factor
XI. Plasma thromboplastin antecedent (AHF C)
XII. Hageman factor
XIII. Fibrin stabilizing factor
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Secondary hemostasis

• Coagulation factors

No Clotting factor Liver Vit K.
I. Fibrinogen
II. Prothrombin
III. Tissue factor (thromboplastin) -
IV. Calcium -
V. Proaccelerin
VII. Proconvertin
VIII. AHF A, vW (-)
IX. Christmas factor (AHF B)
X. Stuart Prower factor
XI. Plasma thromboplastin antecedent (AHF C)
XII. Hageman factor
XIII. Fibrin stabilizing factor ()
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Secondary hemostasis
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Laboratory Diagnosis of Bleeding and Coagulation
Disorders
Prothrombin time (Quick) N 16 s
International normalized ratio N 1 0,2
Activated ProThrombine Time N 35 s
Bleeding Time N 1-6 min
Platelet count N 150 -300 000/ ?l
Thrombine time N lt 22s
Fibrinogen N 1.5-2.77 g/l
Fibrin Degradation Products
D-dimers lt 0,25 mg/L
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Laboratory Diagnosis of Bleeding and Coagulation
Disorders

• 1. Tests of Primary Hemostasis
• Bleeding Time
• Platelet Count
• (Capillary fragility test)

http//www.nlm.nih.gov/medlineplus/bleedingdisorde
rs.html
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Signs of primary hemostasis failure
Ecchymoses
Petechiae
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Signs of primary hemostasis failure
Purpura
Epistaxis Haevy menstrual bleeding Easy
bruising Superficial bleeding into the skin and
mucous membranes
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Laboratory Diagnosis of Bleeding and Coagulation
Disorders

• 2. Tests of Secondary Hemostasis
• Partial Thromboplastin Time (PTT), activated
  partial thromboplastin time (aPTT). (INR)
• Normal range 25-35 seconds
• The PTT is commonly used to monitor heparin
  therapy.
• Prothrombin Time (PT)
• Normal range 11-13 seconds (INR 1 0,2)
• The PT is commonly used to monitor coumarin
  therapy.
• Thrombin Time (TT)
• Normal range lt 22 seconds

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Signs and symptoms of secondary hemostasis failure

• Suffusions

Bleeding into deep tissues (muscles, joints)
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Signs and symptoms of secondary hemostasis failure

• Epistaxis
• Haevy menstrual bleeding
• Easy bruising (deep tissues)
• Bleeding into the deep tissues, muscles, joints
• Delayed bleeding, healing disorders

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Laboratory Diagnosis of Bleeding and Coagulation
Disorders

• 3. Tests of fibrin degradation
• FDP (fibrin degradation products)
• D-dimers

Plazmin     Fibrinogen, Fibrin monomer
Fibrin polymer     FDP
D-dimers
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Coagulation disorders
Stay calm, there is no danger, we have stopped
bleeding

• - Bleeding

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Case 1
What phase of hemostasis is affected?
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What test(s) is (are) most likely to be
performed next?
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Case 1
The patient is thrombocytopenic
indicating a defect of primary
hemostasis.
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32 x109/l
The most likely test to follow bone marrow
examination
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Primary hemostasis defectThrombocytopenia

• Decreased production

• Myelophthisic process
• Ineffective thrombopoiesis
• Bone marrow suppression

Increased destruction or loss

• Dilutional loss
• Non-immune destruction
• Immune destruction

Sequestration

• Hypersplenism
• Hepatosplenomegally

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Case 2
What conclusion can be drawn from this data?
What disorders can lead to these findings?
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Case 2
The increased bleeding time and normal platelet
count ? primary hemostasis function problem.
? platelet function or vascular disorders
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Primary hemostasis defects Thrombocytopathias

• (failure in the adherence, aggregation or
  secretion of thrombocytes)
• ? Inherited
• (v Wilebrand disease,
• Glanzmann thrombasthenia, Hermanský
  Pudlák sy, Chediak-Higashi sy)
• ? Acquired (drugs (aspirin), uremia)

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Primary hemostasis defects Vascular Defects

• (structurally weak vessels or vessels damaged
  by inflammation)
• ? Inherited vessel wall defects (M. Rendu
  Osler), (Connective tissue defects Marfans
  syndrome, M. Ehlers Danloss)
• ? Acquired vessel wall defects (Vitamin C
  deficiency)
• ? Vessel wall inflammation (Immunocomplex
  vasculitis)

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• Morbus Rendu Osler

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• Marfans syndrome

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• Morbus Ehlers - Danloss

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• Scorbut

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Case 3
What conclusions can be drawn from this data?

What tests are likely to be ordered next?
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Case 3

• The abnormal APTT
• defect of the secondary hemostasis, the
  intrinsic pathway

TT Factor concentrations
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Secondary hemostasis defects

• Inherited coagulation defects
• Hemophilia A,B,C
• Parahemophilias
• Hypofibrinogenemia
• Acquired diseases
• Avitaminosis K
• Liver diseases
• Drugs (antibiotics, coumarine derivatives)

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Secondary hemostasis diseases
No Clotting factor Liver Vit K. Diseases
I. Fibrinogen Afibrinogenaemia
II. Prothrombin
III. Tissue factor (thromboplastin)
IV. Calcium
V. Proaccelerin Parahemophilia
VII. Proconvertin
VIII. AHF A, vW Hemophilia A
IX. Christmas factor (AHF B) Hemophilia B
X. Stuart Prower factor
XI. Plasma thromboplastin antecedent (AHF C) Hemophilia C
XII. Hageman factor
XIII. Fibrin stabilizing factor ()
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Primary hemostasis defects - survey
Positive tests Signs
Vascular disorders Vessel wall failure Morbus Rendu Osler Morbus Ehlers Danloss Vitamin C deficiency Vessel wall inflammation Immunocomplex vasculitis RumpelLeede Duke (Platelet count) Petechias Purpura Easy bruising Haevy menstrual bleeding Epistaxis
Platelet defects (number, adherence or aggregation failure) Thrombocytopenias Decreased plt. production Decreased plt. survival Increased pooling of plt. Thrombocytopathias Inherited (v Wilebrands disease, Glanzmanns thrombasthenia) Acquired (drugs, uremia) RumpelLeede Duke (Platelet count) Petechias Purpura Easy bruising Haevy menstrual bleeding Epistaxis
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Secondary hemostasis defects - survey
Coagulopaties Positive tests Signs
Coagulation defects (Deficiencies of one or more clotting factors) Inherited Haemophilias (A,B,C) Parahaemophilias Acquired Vitamin K disorders Liver diseases Abnormal consumption (DIC) APTT Quick FDP ? Concentration of Factors Bleeding into deep tissues Larger ecchymoses Suffusions
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Clinical evaluation of bleeding
Disorders Primary hemostasis Secondary hemostasis
Sex distribution females gt males females lt males
Family history of bleeding rarely positive (except vWD) usually positive
Trauma relationship immediate delayed (often 2 3 days)
Prolonged after cut yes (30 min) no
Direct pressure controls bleeding effective not effective
Petechiae very common not common
Ecchymoses small, multiple none or large and solitary
Hemarthrosis/ deep hematomas no yes
Screening test prolonged bleeding time prolonged PT or PTT
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Patterns of haemostatic tests
Platelet count (Plat.) Bleeding time (BT) aPTT PT
ITP (Idiopathic thrombocytopenic purpura) ? ? N N
Haemophilia A Haemophilia B N N ? N
von Willebrand disease N ? N (or slightly ?) N
DIC ? ? ? ?
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Hypercoagulability states
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Alteration of blood flow
Endothelial injury
Increased coagulability
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Virchows trias 1.

• Endothelial injury
• Trauma or surgery
• Venipuncture
• Heart valve disease or replacement
• Atherosklerosis
• Acute myocardial infarction
• Indwelling catheters
•  

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Virchows trias 2.

• Alteration of blood flow
• Atrial fibrillation, left heart failure
• Immobility
• Long flights
• Venous insuficiency or varicous veins
• Venous obstruction (pelvic tumours)

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Virchows trias 3.

• Increased coagulability
• Increased viskozity (malignancy, pregnancy)
• Protein C S deficiency
• Nephrotic sy
• Hyperfibrinogenemia (metabolic sy)

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• A 25 year old female medical student is found to
  be anemic by her gynecologist. Her Hgb is 7.0
  g/dl, Hct is 21, and her MCV is 60. She reports
  heavy menstrual bleeding throughout her life. She
  also complains of epistaxis and a "funny rash" on
  her lower extremities whenever she takes aspirin.
  Her mother needed several transfusions with
  delivery of each of her children.
• Does this patient have any type of anaemia?
  Which?
• What might be the cause of this state?
• Which type of coagulation abnormality are you
  suspicious for?
• Which other signs and symptoms could she have?
• How would you treat this patient?

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• A 3 year old boy presents with a painful left
  elbow after mild trauma. Evaluation reveals a
  hemarthrosis. The child is adopted so no family
  history is available. The patients mother reports
  no other problems with the child. A PT is normal,
  an aPTT is prolonged.
• Is there primary or secondary hemostasis failure?
  Why?
• What does mean, that PT is normal and aPTT is
  prolonged?
• Which mechanism might cause the prothrombine time
  to be longer?
• Discuss the genetics of the disease.
• Discuss therapy of this disorder.

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Thank you for your attention