Approach to patients with bleeding disorders
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Transcript of Approach to patients with bleeding disorders
AN APPROACH TO AN APPROACH TO PATIENT WITH PATIENT WITH
BLEEDING BLEEDING DISORDERDISORDER
Dr. Salma AfroseAssociate ProfessorDepartment of Hematology
Haemostasis Definition
Spontaneous arrest of bleeding when a small vessel is cut or ruptured
Function • To prevent blood loss from intact vessel • Arrest of bleeding from injured vessel
Mechanism of Normal Haemostasis
Trauma
Vessel Constriction + Shed blood
Coagulation Platelet Adhesion & release of ADP
ThrombinFibrin Platelet aggregation
(unstable plug)
Stable Haemostatic Plug
Haemostatic system is a complex mosaic of activating inhibitory feedback or feed-forward pathways, integrating it’s 5 major components
Vessel Wall Vessel Wall Platelets Platelet Inhibitors Coagulation Fibrinolysis
Blood flow
Production of local Prevention of Haemostasis uncontrolled thrombosis
Damaged Endothelium
Role of Platelet in Haemostasis
vWF
1.Adhesion through vWF
2. Release of ADP, etc
3. Aggregation
4. Clot retraction
Platelet
Endothelial cell
FUNCTIONS OF vWF:
1. vWF mediates platelet adhesion at site of injury 2. Stabilizes FVIII in circulation
Pathways of Haemostasis
XII XIIa
XI XIa
IX IXa
VIIIa Ca2+Phospholipid
VII
Ca2+ Tissue factor
VIIa
X Xa
VIIIa, Ca2+, Phospholipid
Prothrombin (IIa)
Fibrinogen
Fibrinolytic Pathways Plasminogen
Intrinsic Extrinsic XIIa-pa u - pa
t - pa
PAI PAI
PlasminAP
Fibrin FDP
Protease action on Fibrinogen
& FibrinFIBRINOGEN PLASMIN Fibrinogen
degradation products
X,Y,D,E THROMBIN Fibrin monomer Fibrinopeptide A & B FIBRIN PLASMIN Fibrin
degradation[NON CROSS LINKED] products
X,Y,D,E
FACTOR XIII
FIBRIN PLASMIN D dimer[CROSS LINKED] X,Y,D,E
PRIMARY HYPER FIBRINOGENOLYSIS
BLOOD
FREE PLASMIN FIBRINOGEN FDP
ENDOGENOUS ACTIVATOR +PLASMINOGEN
FIBRINOGENOLYSIS
Clinical Distinction Between Disorders of Coagulation & Platelets or Vessel
Finding Disorder of Coagulation
Disorder of Platelets or
Vessels
Petechiae Rare Characteristic
Deep dissecting hematomas
Characteristic Rare
Superficial ecchymoses
Common usually large & solitary
Characteristic usually small & multiple
Hemarthrosis Characteristic Rare
Delayed Bleeding Common Rare
Clinical Distinction Between Disorders of Coagulation & Platelets or Vessel
FindingDisorder of Coagulation
Disorder of Platelets or
vesselBleeding from
superficial cuts & scratches
Minimal Persistent often profuse
Sex of patient80-90% of hereditary forms occur only in
Male
Relatively more common in females
Positive family history Common Rare
HAEMORRHAGIC DISORDER
Definition:These are a group of disorder of widely differing aetiology which have in common tendency to bleed due to defect in the mechanism of haemostasis.
Clinical Features:
1.Spontaneous bleeding in to the skin, mucous membranes & internal tissues.
2.Excessive or prolonged bleeding following trauma or surgery.
3.Bleeding from more than one site.
Classification: Due to Vascular Defects
• Acquired– Simple easy bruising – Senile purpura – Symptomatic vascular
purpura• Henoch-Scholein Purpura • Scurvy • Dysproteinaemia
– Miscellaneous – Orthostatic purpura – Mechanical purpura
• Congenital – Hereditary haemorrhagic
telangiectasia– Ehlar Danlos disease
ClassificationAbnormal Platelet Production • Acquired
– Idiopathic thrombocytopenic purpura
– Drugs & chemicals – Leukemias– Aplastic anaemia– Hypersplenism – Disseminated lupus
erythematosus– Dengue fever
Abnormal Platelet Production • Neonatal & Congenital
– Auto-immune – mothers with chronic ITP
– Drug administration to mother
Classification
• Congenital – Membrane receptor defects – Glanzmann’s Thrombasthenia– Enzyme defect – Phospholipase deficiency – Cycle-oxygenase deficiency – Granuels defects – Storage pool deficiency
• Acquired – Leukemias – Myelodysplasia– Myeloproliferative
disorders – Uraemia – DIC
Due to Disorder of Platelet Function
Classification
• Hereditary – X-linked recessive trait
• Haemophilia-A • Haemophilia-B
– Autosomal recessive trait• Afibrinogenemia• Factor XIII deficiency
– Autosomal Dominant trait • Von-Willbrand Disease
• Acquired – Haemorrhagic disease
of new born – Biliary obstruction – Malabsorption of Vitamin K– Drugs – Liver disease – DIC
Due to Disorder of Coagulation
THROMBOCYTOPENIA
Definition: Thrombocytopenia is defined as a reduction
in peripheral blood platelet count below the normal lower limit of 150 x 109/Liter .
There is no absolute relation between platelet count & occurrence & rate of bleeding.
Bleeding is common –<30000/L but not invariable<10000/L bleeding is usual & often severe
Thrombocytopenia is accompanied by positive tourniquet test & prolonged bleeding time.
Clinical Evaluation • History Purpuric
Coagulation disorder • Hereditary: Onset, positive family history• Acquired: Drug, Viral infection • Drug History• Family History• Clinical feature • Physical examination
Lab Investigation • Hemoglobin percentage • ESR • Total count & Differential count of WBC • Platelet count • Blood film – leukemia, platelet morphology• Bleeding time (BT)• Clotting time (CT)• Prothrombin time (PT)• Activated partial thromboplastin time (APTT)
Special Investigation • Platelet function test • Coagulation factor assay • Fibrinogen Degradation Product (FDP) • Fibrinogen assay • VWF
Immune Thrombocytopenic Purpura
Types of ITP• Primary (Idiopathic)• Secondary
Definition The term idiopathic thrombocytopenic purpura usually refers to thrombocytopenia in which apparent exogenous etiologic factors are lacking & in which diseases known to be associated with secondary thrombocytopenia have been excluded.
Classification
1. Acute Idiopathic Thrombocytopenic Purpura
2. Chronic Idiopathic Thrombocytopenic Purpura
Difference Between Acute & Chronic ITP
Feature Acute ITP Chronic ITPPeak of Age Children of 2-
6 years Adults 20-40 years
Sex predilection
None 3:1 female to male
Antecedent infection
Common 1-3 weeks before
Unusual
Onset of bleeding
Abrupt Insidious
Difference Between Acute & Chronic ITP
Feature Acute ITP Chronic ITP
Hemorrhagic bullae in mouth
Present in severe cases
Usually absent
Platelet count <20,000/ microL 30,000 – 80,000 / microL
Eosinophilia & lymphocytosis
Common Rare
Duration 2-6 weeks rarely longer
> 6 months
Spontaneous remissions
Occur in 80% cases
uncommon
Patho-physiology ITP is caused by platelet specific antibody that bind to patient’s own platelet which are then rapidly cleared from circulation by the mononuclear phagocytic system via macrophage Fc receptor.The auto antibodies formed against platelet gp-IIb/IIIa & gp-Ib/IX.Splenic sequestration account for the shortest survival of platelet in most patients but the liver & RE cells of the bone marrow can play a major role. The Spleen has also been implicated as site of antibody production.
PATHOGENESIS
PLATELET
PLASMA CELL
ANTIBODYCOATEDPLATELET MACROPHAGE
REMOVAL OF ANTIBODYCOATED PLATELETS
Clinical Features • Haemorrhagic manifestation of ITP are of
purpuric type• Severity of bleeding depends on platelet
count • Patient Usually present with cutaneous
purpura, petechiae, echymoses & easy bruising (dry purpura)
On Examination The outstanding feature is absence of physical findings other than those due to anemia:
• Anemia proportionate to the blood loss • Purpuric rashes • Splenomegaly in <10% cases
Lab Investigations: • Hemoglobin percentage – Reduced • CBC:
– WBC count normal / increased during bleeding episodes
–Platelet count reduced • Peripheral Blood film:
–Normocytic normochromic / microcytic anemia
–Platelets are morphologically abnormal; large, small & atypical forms
Lab Investigation• Bleeding time: Raised• Bone Marrow Examination: (in special
circumstances)– Megakaryocyte & their precurosors are
present in normal / increased number & shift to the left
– Other findings are normal – Sometime there is erythroid hyperplasia
if anemia is severe enough
• Special Cases: 1. Not responding to treatment or relapse 2. Patients above 60 years3. Before splenectomy
Diagnosis
• Bleeding manifestation without any physical sign except signs of hemorrhage
• Isolated thrombocytopenia
Differential Diagnosis
• Aplastic anemia• Acute leukemia• Drug induced thrombocytopenia
Treatment• Specific treatment
– Corticosteroid – Immunosuppressive therapy
o Azathioprineo Dexamethasoneo Methylprednisoloneo Ciclosporino Dapsoneo Vincristine
– Splenectomy
Treatment (Contd.)
• Supportive treatment – Blood transfusion– If emergency, platelet transfusion
Thrombotic Thrombocytopenic Purpura
It is a rare disease which is characterized by –– Fever – Thrombocytopenic purpura– Hemolytic anemia – Fluctuating neurological disturbances of
variable nature – Renal failure
It occurs in all age & have the Lab finding like HUS
Hemolytic Uremic Syndrome
DefinitionHemolytic uremic syndrome is a triad of microangiopathic hemolytic anameia, thrombocytopenia & acute renal insufficiency.
Aetiology E.coli 0156:H7 Shigella dysentery serotype-I
(less frequently)
Types
PathogenesisToxin Absorption from Gut in to blood
Attachment to the receptor membrane
Endocytosed Cytolysis Endothelial swelling & desquamation
Platelet & Coagulation activation
Symptoms• Bloody diarrhoea• Severe abdominal pain• Vomiting• Passage of dark red urine which may lead
to Oliguria or anuria
Signs• Anemia • Jaundice • Bleeding manifestation
Lab Findings • Hemoglobin – Decreased• Platelet count – Decreased • Peripheral Blood film - Evidence of hemolysis
present• Serum bilirubin – Increased• Blood urea – Increased• Hemoglobinaemia - Present • Hemoglobinurea – Present• Stool Culture
Treatment• Fluid & electrolyte balance• Dialysis if required • Medication, such as anti-biotic if
indicated • Blood / blood product transfusion if
necessary
Clinical Features • Patient may present with mucosal
bleeding –Epistaxis–Haematuria –Menorrhagia–Melaena
• Intracranial Haemorrhage (rare)
Hemophilia
DefinitionIt is an inherited & X-linked recessive disease
Classification Haemophilia A – Factor VIII
deficiency Haemophilia B – Factor IX deficiency
The daughters of affected males are obligate carriers but the sons are normal.
Clinical FeaturesBleeding tendency usually appear in
infancy In mild cases it may not become
apparent until adolescent or adult life Coagulation factor <1% is severe Coagulation factor 1-5% is moderate Coagulation factor 6-40% is mild
Clinical Feature (contd.) Hemarthrosis Bleeding from skin Tissue bleeding EpistaxisBleeding from central nervous systemUrogenic & gastro-intestinal bleeding
Signs
Anemia Chronic arthritic changes in joints Haematoma
Diagnosis History
Age Sex
History of maternal side Physical findings Clinical findings
InvestigationBleeding time – Normal Platelet count – NormalClotting time – Raised Prothrombin time – Normal APTT – Raised Factor VIII / IX assay - Deficient
Management General Supportive treatment
Rest Local haemostatic measure Replacement therapy
FFP Factor VIII or IX concentrate Blood transfusion
Fibrinolytic inhibitors Aminocapric acid Tranexamic acid
Disseminated Intravascular Coagulation
Definition DIC is an acquired syndrome occurs as a result of inappropriate & excessive activation of haemostatic system that leads to the formation of micro-thrombi throughout the circulation of the body & consumption of platelet, fibrin & coagulation factors
Investigations CBC – Bleeding Time - Raised Platelet Count – DecreasedProthrombin Time – Raised APTT – Raised Fibrinogen Level – Reduced Fibrin Degradation Product – Raised Blood film -
PERIPHERAL BLOOD SMEAR IN DIC
MICROSPHEROCYTE
SCHISTOCYTE
Treatment Treatment of the cause Replacement of coagulation factors &
plateletAnti-coagulant therapy