Bleeding Disorders Lecture Notes PDF

Dr.Mohamed Hamdy Bleeding Disorders Prof.Dr. Mohamed Hamdy Professor of hematology Dr.Mohamed Hamdy 1...

Dr.Mohamed Hamdy Bleeding Disorders Prof.Dr. Mohamed Hamdy Professor of hematology Dr.Mohamed Hamdy 1 1 Dr.Mohamed Hamdy By the end of this lecture1 the student should be able to Recall the physiology of homeostasis as regard platelet ,vascular and coagulation system integration to stop bleeding. Understand the pathophysiology of bleeding disorder in platelet , vascular and coagulation defect. Classify bleeding disorders Differentiate pattern of bleeding disorders due to vascular ,platelet defect vs coagulation defect. Describe Congenital vascular disorders ,hereditary hemorrhagic telangiectasia , Ehlers Danlos and acquired vascular disorder e.g scurvy. Describe conginatal and acquired platlet function dosorders classify causes of thrombocytopenia Describe etiology, clinicl pictures ,investigations and treatment f ITP Recall TTP ,HUS Describe HIT syndrome Dr.Mohamed Hamdy 2 Dr.Mohamed Hamdy Haemostasis Normal bleeding is seen following surgery and trauma and the bleeding stopps eventually by the process of Hemostasis Pathological bleeding occurs when structurally abnormal vessels rupture or when a vessel is breached in the presence of a defect in haemostasias. Dr.Mohamed Hamdy 3 Dr.Mohamed Hamdy Stages of Hemostasis 1. Primary Hemostasis cellular defense – involves the platelet and VWF predominantly goal is rapid cessation of bleeding. vessel injury results in collagen/subendothelial matrix exposure platelets come into contact with damaged vessel wall adhesion: platelets adhere to subendothelium via VWF activation: platelets are activated resulting in integrin activation, shape change, and granule release aggregation: activated GPIIbIIIa on platelets binds soluble ligands, which results in aggregation and the formation of a localized platelet plug Dr.Mohamed Hamdy 4 Dr.Mohamed Hamdy 2. Secondary Hemostasis platelet plug is reinforced by production of a fibrin clot extrinsic (initiation) pathway: initiation of coagulation in vivo intrinsic (amplification) pathway: amplification once coagulation has started via positive feedback the intrinsic and extrinsic pathways converge onto the common pathway, →thrombin generation → fibrin formation 3. Fibrin Stabilization conversion from a soluble to an insoluble, cross-linked clot 4. Fibrinolysis once healing is initiated, clot dissolution is mediated by the fibrinolytic system Dr.Mohamed Hamdy 5  Three phases of Haemostasis Dr.Mohamed Hamdy 6 Injury +30 sec Coagulation phase Injury Platelet phase A complex series of steps produces a Vascular phase fibrin clot Platelets attach to the injured endothelium, stick Blood vessels to one another, and contract in response become activated to injury Dr.Mohamed Hamdy Dr.Mohamed Hamdy Intrinsic XII XIIa Extrinsic XI TF VII XIa IX IXa VIIa VIIIa TF X Xa X Va Common II IIa Fibrinogen Fibrin Dr.Mohamed Hamdy 7 Dr.Mohamed Hamdy Causes of bleeding disorder bleeding disorders are divided into the following groups: 1. vascular defects 2. abnormalities of platelet number or function 3. clotting factor deficiencies 4. combinations of the three above mentioned disorders. 1. liver disease 2. disseminated intravascular coagulation (DIC) 3. chronic kidney disease. Dr.Mohamed Hamdy 8 Dr.Mohamed Hamdy Vascular Defects Platelet Disorders Coagulation Disorders Congenital: Decreased marrow production: Congenital:.Haemophilia,. Connective tissue disease (eg. Aplastic anaemia.von Willebrand’s disease Ehlers–Danlos syndrome). Megaloblastic anaemia. Marrow infiltration (eg leukaemia, myeloma),. Marrow suppression (cytotoxic drugs, radiotherapy). Acquired: Excess destruction:. Acquired:.Anticoagulants,. Senile purpura. ITP. liver disease. Infection (eg meningococcal).Other autoimmune eg SLE, CLL.. vitamin K deficiency..Steroids. Drugs, eg heparin.viruses. Scurvy.TTP or HUS. Hypersplenism Poorly functioning platelets: NSAIDS, and sulphonaylureas Dr.Mohamed Hamdy 9 Dr.Mohamed Hamdy The pattern of bleeding is important Vascular. and platelet disorders prolonged bleeding from cuts, skin bleeding (easy bruising and purpura) bleeding from mucous membranes (epistaxis, bleeding from gums, menorrhagia). Coagulation disorders delayed bleeding into joints and muscle Dr.Mohamed Hamdy 1 Dr.Mohamed Hamdy Clinical signs Disorders of Disorder of platelets coagulation or vessles Petechiae Rare Characteristics Ecchymoses Common, large Characteristics, small Bleeding from Minimal Persistent superficial cuts Delayed bleeding Common Rare Deep hematomas Characteristics Rare Hemothrosis Characteristics Rare Dr.Mohamed Hamdy 1 Dr.Mohamed Hamdy vascular Dr.Mohamed Hamdy 12 Dr.Mohamed Hamdy Vessel wall abnormalities Vessel wall abnormalities may be: senility : senile purpura Congenital (hereditary haemorrhagic telangiectasia , Ehler Danlos) acquired, as in a vasculitis or scurvy. Dr.Mohamed Hamdy 13 Dr.Mohamed Hamdy Hereditary haemorrhagic telangiectasia AD disease mutations in the angiogenic genes stimulator Telangiectasia and small aneurysms on fingertips, face and tongue , nose, lung and GIT. Patients present with recurrent bleeds, particularly epistaxis iron deficiency due to occult gastrointestinal bleeding. Treatment can be difficult because of the multiple bleeding points. Dr.Mohamed Hamdy 14 Dr.Mohamed Hamdy Vascular Ehlers–Danlos disease AD disorder caused by a defect in type 3 collagen →fragile blood vessels and organ membranes, leading to bleeding and organ rupture. Limited Classical joint hypermobility. skin and facial changes ( large eyes, small chin, sunken cheeks, thin nose and lips). The diagnosis should be considered when there is a history of bleeding but laboratory tests are normal. Dr.Mohamed Hamdy 15 Dr.Mohamed Hamdy Scurvy Vitamin C deficiency affects the normal synthesis of collagen and results in a bleeding disorder. characterized by petechial haemorrhage, bruising and subperiosteal bleeding. The key to diagnosis is the dietary history Dr.Mohamed Hamdy 16 Dr.Mohamed Hamdy Platelet disorders Dr.Mohamed Hamdy 17 Dr.Mohamed Hamdy Approach to platelet disorders 1-Decreased platelet function (normal count) 2-Low platelet count Dr.Mohamed Hamdy 18 Dr.Mohamed Hamdy Platelet disorders 1-Platelet function disorders(normal count) Congenital Von willbrand disease (most common hereditary hemorrhagic disease) Glanzmann’s thrombasthenia (IIb/IIIa):defective aggregation Bernard–Soulier disease (Ib):defective adhesion Storage pool disorders :defective Secretion Acquired Iatrogenic from the use of aspirin, clopidogrel, dipyridamole and the IIb/IIIa inhibitors to prevent arterial thrombosis. systemic diseases as Renal failure, Liver disease, Diabetes, Hyperglobulinemias Dr.Mohamed Hamdy 19 Dr.Mohamed Hamdy Bernard Soulier Syndrome Glanzmann's Thrombasthenia Dr.Mohamed Hamdy Dr.Mohamed Hamdy Platelet disorders 2-Thrombocytopenia(low count) Thrombocytopenia is defined as a platelet count below the lower limit of normal (ie,