Bleeding Disorders PDF

Bleeding disorders Dr.Dhafar Kamil  Bleeding generally indicates extravasation of blood following blood vessel rupture; usually it is precipitated by trauma or surgery. spontaneous bleeding and severe bleeding following insignificant injury is usually seen in bleeding disorders. Abnormal b...

Bleeding disorders Dr.Dhafar Kamil  Bleeding generally indicates extravasation of blood following blood vessel rupture; usually it is precipitated by trauma or surgery. spontaneous bleeding and severe bleeding following insignificant injury is usually seen in bleeding disorders. Abnormal bleeding may result from:- 1.Vascular disorders. 2.Defect in platelet number or function. 3.Defect in blood coagulation. 4-Local causes **The pattern of bleeding depend on the cause, defect in blood vessels or in platelets usually produce skin and mucous membrane bleeding ,while defect in coagulation usually produce joint and soft tissue bleeding   Vascular disorders:- group of conditions characterized by easy bruising , the underlying abnormality is either in the vessel or in the perivascular connective tissues.in most cases the bleeding is not severe mainly petichiae and ecchymosis. In vascular disorders the standard screening tests of hemostasis are normal. Vascular disorders may be inherited or acquired: 1. inherited vascular disorders :- - Like hereditary hemorrhagic telangectasia Connective tissue disorders like Ehler – Danlos syndrome  2- Acquired vascular disorders:- a. Easy bruising may occur in healthy female at child bearing age and is benign. b.Senile purpura due to atrophy of the supporting tissue of cutaneous blood vessels. c. Many bacterial, viral, rickettsial infections may cause purpura either caused by the organism or by immune complex formation. d.Henoch- Schonlen Purpura :- this disease is usually seen in children and usually follows acute infection, it is characterized by purpuric rash, itching, and edema usually prominent on buttocks and extensor surfaces of lower legs , haematuria, abdominal pain , it is self limiting but some patients develop renal failure. e. Scurvy :- vitamin C deficiency leads to defective collagen f. Steroid therapy: - long term steroid therapy may cause purpura.  Thrombocytopenia:- Thrombocytopenia is defined as subnormal number of platelets in the circulation, usually below 100× 109/L, the risk of bleeding is increased with the decline in platelet number. Bleeding resulting from thrombocytopenia is mainly petichiae, and mucosal bleeding, Thrombocytopenia may be  mild when platelet level is > 80×109/L ,  Or moderate when platelets are between 20-80 ×109/L  Or severe when the count drop to< 20 ×109/L.  The main causes of thrombocytopenia are:- 1-failure of platelet production :- mainly as a part of generalized bone marrow failure due to cytotoxic drugs , radiation ,aplastic anemia , leukemia , marrow infiltration with malignancy, HIV infection, myelofibrosis. 2-increased platelet consumption :- a. immune mechanism :- such as in Idiopathic immune thrombocytopenic purpura. Viral infection. Drug induced. Post transfusion purpura. a. non- immune mechanisms (increase platelet consumption by forming disseminated micro thrombi in the small blood vessles)  Disseminated intravascular coagulation.  Thrombotic thrombocytopenic purpura.  Hemolytic uraemic syndrome. 3-Abnormal distribution of platelets: - as in spleenomegally. 4-Dilutional loss as in massive transfusion of stored blood to a bleeding patient. Idiopathic immune thrombocytopenic purpura :(ITP) ITP is an autoimmune disease mediated by Ab directed against platelets, platelets opsonized (coated) with those antibodies will be destroyed by the mononuclear phagocytic cells mainly in the spleen. ITP may be divided into:- a. Acute ITP. b. Chronic ITP.  Chronic ITP :- is a common disorder with a higher incidence in females between 15-50 years of age , it is the most common cause of solitary thrombocytopenia (with out anemia or leucopenia ). It is usually idiopathic but may be seen in association with other diseases like SLE , HIV infection, chronic lymphocytic leukemia, Hodgkin,s lymphoma. Pathogenesis: - platelets are destroyed by auto antibodies (usually IgG ) that result in premature removal of platelets from the circulation by macrophages mainly in the spleen. The Ab is directed to glycoprotein IIb/IIIa or glycoprotein Ib on the surface of platelets. Normally the platelet life span is 7-10 days, in ITP it is reduced to few hours. The number of megakaryocytes and platelet production is increased up to 5 times of normal.  Diagnosis:- 1. Platelet count is low , hemoglobin and WBC count are normal unless there is iron deficiency anemia due to blood loss, the blood film show decrease number of platelets with some large forms. 2. Bone marrow showed increased number of megakaryocytes. Other hemopoietic elements are normal. however bone marrow examination is not done routinely , it is usually indicated for:-  Patients who fail to respond or relapse after first line therapy.  The presence of atypical features.  Before splenectomy. 3-Tests to detect the antibodies against platelet glycoproteins.  Acute ITP :- most common in children and in about 75% of patients the disease follows vaccination or infection (infectious mononucleosis, chicken pox). Acute ITP is mostly due to non-specific immune complex deposition on platelets, usually the disease remit spontaneously and 5-10% of cases become chronic (. Differences in clinical presentation between acute and chronic ITP Clinical feature Acute ITP Chronic ITP Peak age 2-8 y 15-50 y Male :female 1:1 1:1.7 Onset abrupt insidious duration weeks Months may be years Associated disorders Precipitated by viral Idiopathic or it can be infection or vaccination secondary pathogenesis Immunecomplex Auto Ab against platelet deposition glycoproteins Treatment  Non-immune mediated platelet consumption (consumptive coagulopathy):- Group of conditions characterized by wide spread activation of the coagulation system with the resulted consumption of platelets and the coagulation factor by wide spread microthrombi formation resulting in decrease in their number of platelets and the amount of coagulation factors in the circulation. These disorders include:-  1-Thrombotic thrombocytopenic purpura :- whether familial or acquired in TTP there is defect in ADAMS 13 which is a metaloprotease responsible for transforming the large forms of VWF into the functional small forms , defect in this protease will result in the accumulation of these abnormal large forms that are highly thrombogenic that would result in widespread thrombus formation in small blood vessels and the resulted in consumption and reduction in the number of platelets in the circulation. The wide spread thrombi will also act like a sieve causing fragmentation of the RBC (fragmentation hemolysis) 2-Hemolytic uremic syndrome:- a form of consumptive coagulopathy usually seen in children, the kidneys are mainly affected and there is usually history of diarrhea mostly caused by Coli infection. 3-Disseminated intravascular coagulation:-it is widespread intravascular deposition of fibrin that leads to consumption of coagulation factors and platelets. DIC occur as a consequence of many disorders which release procoagulant material into the circulation or causes widespread endothelial damage and platelet aggregation., of these conditions:-  Sepsis and severe Infections.  Severe trauma and tissue injury like burn.  Malignancy: - as solid tumors and haematological malignancies (e.g. acute promyelocytic leukaemia).  Obstetric complications like intrauterine death.  Severe toxic or immunological reactions: - like snake bites, severe transfusion reactions and transplant rejection.  whatever the cause is the resultant activation of the coagulation system will result in widespread thrombi formation with the reduction in the number of platelets (thrombocytopenia) and also of the coagulation factors with prolongation of the coagulation tests(PT, PTT, TT ) , the fibrinogen level is low , and the fibrin degradation products are increased due to excessive activation of the fibrinolytic system.  Platelet function defect:- Platelet function defects are suspected in patients with skin and mucous membrane bleeding with a normal platelet count , the bleeding time is prolonged which is helpful in differentiating it from vascular disorders , the diagnosis is confirmed by specific platelet function tests , it may be hereditary or acquired. 1.inherited platelet function defects:- Bernard- Soulier syndrome :- an autosomal recessive disorder characterized by the presence of giant platelets in blood film , prolonged bleeding time. The disorder is due to quantitative or qualitative deficiency of GP Ib Glanzmann,s thrombosthenia :- an autosomal recessive disorder in which there is deficiency of GP IIb/IIIa which act as a receptor for fibrinogen, 2-acquired platelet function defects :- A-antiplatelet drugs :- Aspirin is the most common drug, it produces an abnormal bleeding time, and it causes inhibition of cyclo-oxygenase enzyme. Other drug is Dipyridamole which inhibits platelets aggregation by blocking adenosine uptake(ADP antagonist). Clopidogrel that inhibits ADP binding. B-Uremia: - due to the presence of toxic substances that interfere with platelet function. C-Hyperglobulinaemia: - as in Multiple Myeloma, the paraprotein may interfere with platelet adhesion, release reaction and aggregation. D-Myeloproliferative and Myelodysplastic syndromes.