1 bleeding disorders k. bernášková. 2 the hemostatic system
TRANSCRIPT
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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
(a) Platelet adhesion
(b) P. aggregation
(c) P. activation
1. Vasoconstriction
2. Primary clot formation
sympaticus
serotonin
TXA2
axo-axonal reflex
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Secondary hemostasisCoagulation 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 hemostasisCoagulation 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
Patient IDDate
Special Studies
PTCont.
INRAPTTBTPlat.TTFibr.FDPD-Dimer
HEMOSTASIS
Prothrombin time (Quick) N = 16 s
International normalized ratio N = 1 ± 0,2Activated ProThrombine Time N = 35 sBleeding Time N = 1-6 minPlatelet count N = 150 -300 000/ lThrombine time N < 22sFibrinogen N = 1.5-2.77 g/l
Fibrin Degradation ProductsD-dimers < 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/bleedingdisorders.html
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Signs of primary hemostasis failure
Petechiae Ecchymoses
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Signs of primary hemostasis failure
PurpuraEpistaxis
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 = < 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
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
Coagulation disorders
- Bleeding
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Stay calm, there is no danger, we have stopped bleeding
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Case 1
Patient IDDate
Special Studies
PTCont.
INRAPTTIBTPlat.TTFibr.FDPD-Dimer
HEMOSTASIS
12.1 Sec.12.4 Sec.
1.130.0 Sec.
5.5 Min.32 x109/L
Patient IDDate
Special Studies
PTCont.
INRAPTTIBTPlat.TTFibr.FDPD-Dimer
HEMOSTASIS
12.1 Sec.12.4 Sec.
1.130.0 Sec.
5.5 Min.32 x109/L
What phase of hemostasis is
affected?
What test(s) is (are) most likely to be performed
next?
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Case 1
Patient IDDate
Special Studies
PTCont.
INRAPTTIBTPlat.TTFibr.FDPD-Dimer
HEMOSTASIS
12.1 Sec.12.4 Sec.
1.130.0 Sec.
5.5 Min.32 x109/L
Patient IDDate
Special Studies
PTCont.
INRAPTTIBTPlat.TTFibr.FDPD-Dimer
HEMOSTASIS
12.1 Sec.12.4 Sec.
1.130.0 Sec.
5.5 Min.32 x109/L
The patient is thrombocytopenic
indicating a defect of primary
hemostasis.
The most likely test to follow: bone marrow examination
32 x109/l3
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Primary hemostasis defectThrombocytopenia
Decreased production Myelophthisic process
Ineffective thrombopoiesis
Bone marrow suppression
Dilutional loss
Non-immune destruction
Immune destruction
Hypersplenism Hepatosplenomegally
Sequestration
Increased destruction or loss
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Case 2
Patient IDDate
Special Studies
PTCont.
INRAPTTBTPlat.TTFibr.FDPD-Dimer
HEMOSTASIS
12.1 Sec.12.4 Sec.
1.130.0 Sec.
>15 Min.302 x109/L
What conclusion can be drawn from this data?
What disorders can lead to these findings?
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Case 2
Patient IDDate
Special Studies
PTCont.
INRAPTTBTPlat.TTFibr.FDPD-Dimer
HEMOSTASIS
12.1 Sec.12.4 Sec.
1.130.0 Sec.
>15 Min.302 x109/L
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,
Heřmanský – 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: Marfan‘s 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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Marfan‘s syndrome
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Morbus Ehlers - Danloss
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Scorbut
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Case 3Patient IDDate
Special Studies
PTCont.
INRAPTTBTPlat.TTFibr.FDPD-Dimer
HEMOSTASIS
12.1 Sec.12.4 Sec.
1.160.5 Sec.
6.0 Min.332 x109/L
What conclusions can be drawn from this data?
What tests are likely to be ordered next?
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Case 3Patient IDDate
Special Studies
PTCont.
INRAPTTIBTPlat.TTFibr.FDPD-Dimer
HEMOSTASIS
12.1 Sec.12.4 Sec.
1.160.5 Sec.
7.0 Min.332 x109/L
The abnormal APTT defect of the secondary hemostasis, the intrinsic pathway
TTFactor concentrations
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Secondary hemostasis defects
Inherited coagulation defectsHemophilia A,B,CParahemophiliasHypofibrinogenemia
Acquired diseasesAvitaminosis 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 deficiencyVessel wall inflammation Immunocomplex vasculitis Rumpel–
LeedeDuke(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 Wilebrand‘s disease, Glanzmann‘s thrombasthenia) Acquired (drugs, uremia)
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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)
APTTQuick
FDP Concentration
of Factors
• Bleeding into deep tissues• Larger ecchymoses• Suffusions
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Clinical evaluation of bleeding Disorders Primary
hemostasisSecondary hemostasis
Sex distribution females > males females < 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 AHaemophilia B
N N N
von Willebrand disease N
N (or slightly )
N
DIC
Hypercoagulability states
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Endothelial injury
Alteration of blood flow
Increased coagulability
Virchows trias 1.
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Endothelial injury
•Trauma or surgery•Venipuncture•Heart valve disease or replacement•Atherosklerosis •Acute myocardial infarction•Indwelling catheters
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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Change (Disturbance): Reason: Example:
Disturbances of the flow Platelets not kept away from the wall
Turbulent flow stenosis
Stasis Atrial fibrillation, immobilisation, failing valves in veins
Vessel wall damage
Endothelial activation, decreased smoothness
Mechanical Hypertension, atherosclerosis; injury
Chemical Endothelial dysfunction sy in diabetes, sepsis; homocystein; inflammation
Platelet activity Increased stickiness due to Ab Antiphospholipid sy in LE
activity adrenalin, chronic stress, smoking
Coagulation factors
Increased concentration
Severe dehydration Chronic inflammation, metabolic sy, neoplasias
Dysballance Nephrotic sy
Anticoagulation factors
Decreased
Concentration
Decreased formation of protein C + S in liver failure Increased loss - of AT3, plasminogen (nephrotic sy)
Sensitivity to Protein C + S in Leyden V. factor Activity of Protein C + S, AT3 (Contraceptive drugs)
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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.
1. Does this patient have any type of anaemia? Which?
2. What might be the cause of this state?
3. Which type of coagulation abnormality are you suspicious for?
4. Which other signs and symptoms could she have?
5. 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.
1.1. Is there primary or secondary hemostasis failure? Why? Is there primary or secondary hemostasis failure? Why?
2.2. What does mean, that PT is normal and aPTT is prolonged?What does mean, that PT is normal and aPTT is prolonged?
3.3. Which mechanism might cause the prothrombine time to be longer?Which mechanism might cause the prothrombine time to be longer?
4.4. Discuss the genetics of the disease.Discuss the genetics of the disease.
5.5. Discuss therapy of this disorder.Discuss therapy of this disorder.
Thank you for your attention
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