Anemias and Haemophilia Notes PDF

Anemias and Heamophilia DEFINITION  Anemia is said to be present when the hemoglobin level in the blood is below the lower limit of normal range for the age and sex of the individual.  Thus it is said to be present when the adult male hemoglobin is less than 13 gm/dl, and adult femal...

Anemias and Heamophilia DEFINITION  Anemia is said to be present when the hemoglobin level in the blood is below the lower limit of normal range for the age and sex of the individual.  Thus it is said to be present when the adult male hemoglobin is less than 13 gm/dl, and adult female hemoglobin is less than 12 gm/dl. CLINICAL FEATURES  Symptoms of anemia are due to:  a- The anemia itself.  b- The underlying disorder causing the anemia. CLINICAL FEATURES  The hemoglobin level at which symptoms of anemia develop depends on 3 main factors  i-Speed of onset : Rapidly progressive anemia causes more symptoms than anemia of slow onset.  ii Age : The elderly tolerate anemia less than young because of the poor cardiovascular compensation.  iii-Severity : Mild anemia often produces no symptoms (10 to 12 & 13 gm/dl), but these symptoms occur in moderate anemia (7 to 10 gm/dl). Symptoms and signs 1- Fatigue and weakness. 2- Pallor is the most prominent and characteristic sign. 3- Nervous system : These include dizziness, fainting, headache, tinnitus, lack of concentration, and numbness. 4- Reproductive system : Menstrual disturbances as amenorrhea or menorrhagia Symptoms and signs  5- Cardiovascular system :  * exertional dyspnea.  * Angina pectoris in old patients.  * Intermittent claudication.  * Haemic murmurs.  * heart failure.  * Bounding pulse  * ECG changes Symptoms and signs  6- Renal system :  Slight proteinuria, impairment of concentrating power of the kidney and aggravation of renal failure.  7- Gastrointestinal system  Anorexia, flatulence, nausea and constipation may occur but no weight loss from the anaemia per se.  8- Impairment of liver function in severe anaemia. Approach to patient with anemia  3 questions must be answered  1- Is the patient anemic or not?  2- what is the type of anemia ?  3- What is the cause of the anemia ? Question 1  1- Is the patient anemic ?  This is suspected from the signs and symptoms listed and mentioned before. Obviously these are not specific to anemia. Question 2  2- What is the type of anaemia ?  This is indicated by red cell counts, Hb. concentration, red cell indices as well as leucocytic and platelet counts.  The morphologic classification` of anemia includes 3 types; microcytic, normochromic and macrocytic. Question 2  2- What is the type of anaemia ?  (i) Microcytic hypochromic anaemias :  Mean corpuscular volume (MCV) is 80 fl, mean corpuscular hemoglobin (MCH) 27 pg and mean corpuscular hemoglobin concentration (MCHC)  30 gm/dl.  The most important causes are :  * Iron deficiency anaemia.  * Thalassemias.  * Sideroblastic anaemia.  * Lead poisoning.  * Chronic diseases. MICROCYTIC ANEMIA Question 2  2- What is the type of anaemia ?  (ii) Normocytic normochromic anaemias :  Here the MCV, MCH, and MCHC are within normal range. Causes include :  * Acute haemorrhage.  * Haemolytic anaemias.  * Aplastic anaemias.  * Bone marrow infiltrations.  * Chronic renal failure.  * Chronic disease. Question 2  2- What is the type of anaemia ?  (iii) Macrocytic anaemias :  Here the MCV is 90 fl.  The red cells are usually normochromic. These include:  Megaloblastic anaemias.  Non-megaloblastic macrocytic anaemias  liver disease, myelodysplasia. MACROCYTIC ANEMIA Question 3  3-What is the cause of anaemia? I- Decreased red cell production:  Stem cell failure  1. Aplastic anemia 2. Anemia of leukemia and myelodysplastic syndromes  Progenitor erythroid cell failure 1. Pure red cell aplasia 2. Anemia of organ failure e.g. chronic renal failure  Precursor cell failure (dyshemopoietic anemia)  1. Iron deficiency anemia 2. Megaloblastic anemia 3. Myelodysplastic syndromes (MDS) Question 3  II- Increased red cell destruction or loss:  Hereditary  1. Membrane defects e.g -hereditary spherocytosis  2. Hemoglobinopathies e.g. thalassemia, sickle cell anemia  3. Enzyme defectse.g.G6PD deficiency  4. Acquired Immune hemolytic anemia Hypersplenism Microangiopathic hemolytic anemia e.g. DIC Acute blood loss fat Paroxysmal nocturnal hemoglobinuria (PNH)  ANAEMIA RC Indices(volume) MVC MVC Normal MVC Macrocytic Microcytic Normocytic  Hypochromic Microcytic Anaemia Serum Iron Serum Fe Serum Fe Normal Serum Ferritin serum iron BM Sideroblast Thalassemia Iron Anemia of deficiency chronic anemia Hemoglobinopathies Sideroblastic illness anaemia Angular stomatitis & glossitis Spooning of nails in iron deficiency.  Normochromic Anaemia Reticulocytes N/  Renal BM disease Hemorrhagge Endocrine MDS Hemolysis Hepatic Infiltration AA  Macrocytic Anaemia Reticulocytosis No Yes Is BM megaloblastic Prior Hge Yes No Hypothyroid Vit B12/Folate def Prior hemolysis MDS Drug induced Approach of bleeding disorder  Three important factors for coagulation 3. 2. 1.Blood vessel Screening tests  CBC (plat. count)  Bleeding time  Clotting time (PT, PTT) Evaluation of platelet disorders: 1. Platelets Count and morphology 2. Bleeding time 3. Platelet adhesion 4. Platelet aggregation by using ADP, collagen, prostaglandin and Ristocetin. Purpura and petechiae Coagulation and clot stabilization Heamarthrosis Hemophilias:  They are hereditary bleeding disorders caused by deficiencies of coagulation factors VIII or IX.  The extent of factor deficiency determines the probability and severity of bleeding  The diagnosis is suspected in an elevated partial thromboplastin time and normal prothrombin time and platelet count.  It is confirmed by specific factor assay. Hemophilias:  Hemophilia A  Factor VIII deficiency is x-linked occurring in1:5000-10,000 live male births.  In severe cases the missing factor is less than 1%.(bleeding occurs spontaneously) Hemophilia A  Clinical picture:  Bleeding may occur anywhere in patients with hemophilia  Bruising, soft tissue bleeding, joint bleeds (hemoarthrosis), and other sites of musculoskeletal bleeding  Epistaxis, oral, gastrointestinal bleeding: can occur from numerous oropharyngeal sites such as the nose, oral mucosa, and gingiva; sometimes this type of bleeding follows minor trauma or dental procedures  Hematuria is a frequent manifestation of severe hemophilia.  Bleeding may occur after surgery, dental extraction or trauma. Hemophilia A  Diagnosis:  A prolonged activated partial thromboplastin time (aPTT), normal Prothrombin time and platelet count.  Measurement of the factor activity level (factor VIII in hemophilia A) Hemophilia A  Treatment  Generally avoid intramuscular injections  Plan surgical procedures carefully  Treat bleeding episodes promptly  Desmopressin (vasopressin analogue): IV or intranasal, useful in the treatment of mild to moderate cases, it can increase factor VIII 2-3folds  Antifibrinolytic agents (tramenexamic acid, aminocaproic acid) are useful adjunctive therapy for mucosal bleeding particulary dental extraction, but are contraindicated if the patient has hematuria Hemophilia A  Treatment  Factor VIII concentrate is needed in severe cases or in the presence of bleeding.  It is either prepared from plasma that is virally inactivated or recombinant.  In the absence of concentrates, cryoprecipitate can be used, though the risks of viral infections are very high.  Fresh frozen plasma should be used only if rapid replacement therapy is necessary and factor concentrate is unavailable  Recombinant human factor VIII Hemophilia B (CHRISTMAS DISEASE)  It is less common and results from factor IX deficiency.  X — linked recessive disorder  Treatment: Hemophilia B is treated with factor IX or other hemostatic therapies such as antifibrinolytic agents and/or topical therapies.  Fresh frozen plasma should be used only if rapid replacement therapy is necessary and factor concentrate is unavailable  A recombinant factor IX fusion protein