Clinical Pharmacy in Haematology Spectrum of haematological diseases Deficiency anaemias Deficiency anaemias Disorders of haemoglobin structure Disorders of haemoglobin structure Haemolytic structure Haemolytic structure Aplastic anaemia Aplastic anaemia Haematological malignancies: leukaemias and lymphomas Haematological malignancies: leukaemias and lymphomas (all aspects of management, including bone marrow transplantation) Congenital and acquired bleeding disorders Congenital and acquired bleeding disorders Thromboembolic disorders and anticoagulation Thromboembolic disorders and anticoagulation Transfusion medicine Transfusion medicine Haematological problems associated with perinatal care; Haematological problems associated with perinatal care; intensive care; renal medicine, organ transplantation, orthopaedic and vascular surgery (in adults). The main symptoms of hematology: Weakness Weakness Drowsiness Drowsiness Dizziness Dizziness Heartbeat Heartbeat Shortness of breath Shortness of breath Loss of appetite Loss of appetite Increased liver, spleen and lymph nodes Increased liver, spleen and lymph nodes Heartburn tip of the tongue, redness and ulcers, smoothing papillaes Heartburn tip of the tongue, redness and ulcers, smoothing papillaes Bruises on the body, skin hemorrhages (petechiae, purpura). Bruises on the body, skin hemorrhages (petechiae, purpura). Bleeding from the mucous membranes, bleeding in the mouth cavity. Itching of the skin. Pale color of skin and mucous. Power color face. Yellow color of skin and mucous (ikterychnist) Swelling of the skin and subcutaneous fiber (hidremiya). Pain during tapping on the bones Anemic syndrome weakness weakness fatigue fatigue tinnitus tinnitus dizziness dizziness shortness of breath shortness of breath heartbeat heartbeat pale skin and mucous membranes pale skin and mucous membranes Objective symptoms Atrophy of the papillae of the tongue, angular stomatitis Atrophy of the papillae of the tongue, angular stomatitis Pale conjunctiva Sideropenic syndrome Changes in skin, hair and nails Changes in skin, hair and nails Changes in the musculoskeletal system Changes in the musculoskeletal system Changes of mucosa of the digestive tract Changes of mucosa of the digestive tract Changes in airway mucosa Changes in airway mucosa Changes in the immune system Changes in the immune system Changes in taste and smell perception Changes in taste and smell perception Changes in thermoregulation Changes in thermoregulation Changes in emotional state Changes in emotional state Dystrophic changes of internal organs Dystrophic changes of internal organs Hemorrhagic syndrome hemorrhages in the skin and internal organs of one or more locations that are repeated regularly, spontaneously or after influence of minor injuries. hemorrhages in the skin and internal organs of one or more locations that are repeated regularly, spontaneously or after influence of minor injuries.Reasons: toxemia of capillary vessels; toxemia of capillary vessels; thrombocytopenia; thrombocytopenia; change blood chemistry. change blood chemistry. Hemorrhagic syndrome Polycythemic syndrome: Characterized by high erythrocytosis, increased volume of circulating blood and its viscosity. Main symptoms: strengthen color of the skin and mucous membranes; strengthen color of the skin and mucous membranes; congestion of internal organs; congestion of internal organs; headache; headache; thrombosis; thrombosis; sharp increase of the number of red blood cells; sharp increase of the number of red blood cells; reticulocytosis, neutrophilic leukocytosis; reticulocytosis, neutrophilic leukocytosis; increase in blood viscosity. increase in blood viscosity. Compensatory polycythemia - polycythemia. Independent process - erythremia. Disseminated intravascular coagulation (DIC) a bleeding disorder characterized by reduction in the elements involved in blood clotting due to their use in widespread clotting within the vessels. In the late stages, it is marked by profuse hemorrhaging. a bleeding disorder characterized by reduction in the elements involved in blood clotting due to their use in widespread clotting within the vessels. In the late stages, it is marked by profuse hemorrhaging. DIC can occur in the following conditions Solid tumors and hematologic malignancies (particularly acute promyelocytic leukemia)acute promyelocytic leukemia Obstetric complications: abruptio placentae, pre- eclampsia or eclampsia, amniotic fluid embolism, septic abortion Obstetricabruptio placentaepre- eclampsia Massive tissue injury: severe trauma, burns, hyperthermia, rhabdomyolysis, extensive surgerytraumahyperthermiarhabdomyolysis Sepsis or severe infection of any kind: bacterial (Gram- negative andGram-positive sepsis), viral, fungal, or protozoan infectionsGram- negativeGram-positive Transfusion reactions (i.e., ABO incompatibility hemolytic reactions)ABO incompatibility hemolytic reactions Severe allergic or toxic reactions (i.e. snake or viper venom) Giant hemangiomas (Kasabach-Merritt syndrome)hemangiomasKasabach-Merritt syndrome Large aortic aneurysmsaortic aneurysms Anemia reduction below normal of the number of er ythrocytes, quantity of hemoglobin, or the volume of packed red cells in the blood; a symptom of various diseases and disorders reduction below normal of the number of er ythrocytes, quantity of hemoglobin, or the volume of packed red cells in the blood; a symptom of various diseases and disorders Iron deficiency anemia a form of anemia due to lack of iron in the diet or to iron loss as a result of chronic bleeding Characterized by: Redistribution of iron in macrophage cells system which is activated by inflammatory process Redistribution of iron in macrophage cells system which is activated by inflammatory process Reducing of the using of iron in the bone marrow Reducing of the using of iron in the bone marrow Shortening the life of red blood cells Shortening the life of red blood cells Reducing of the production of erythropoietin Reducing of the production of erythropoietin Pernicious anemia A severe anemia most often affecting older adults, caused by failure of the stomach to absorb vitamin B 12 and characteriz ed byabnormally large red blood cells, gastrointestinal distur bances, and lesions of the spinal cord. Characterized by the presence of 3 syndromes: anemic syndrome anemic syndrome Lesions of the digestive system (gastrointestinal tract atrophy, glossitis) Lesions of the digestive system (gastrointestinal tract atrophy, glossitis) Neurological syndrome (myeloses: polyneuropathy, vibration and abuse positional sensitivity, possible paresis and paralysis, mental disorders) Neurological syndrome (myeloses: polyneuropathy, vibration and abuse positional sensitivity, possible paresis and paralysis, mental disorders) Leukemia a progressive, malignant disease of the blood- forming organs, marked by distorted proliferation and development of leukocytes and their precursors in a progressive, malignant disease of the blood- forming organs, marked by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Acute leukemialeukemia in which the involved cell line shows little or no differentiation, usually consisting of blast cells; it comprises two types, acute lymphocytic leukemia and acute differentiation, usually consisting of blast cells; it comprises two types, acute lymphocytic leukemia and acute myelogenous leukemia acute lymphocytic leukemia acute lymphocytic leukemia characterized by anemia, fatigue, weight loss, easy bruising, thrombocytopenia, granulocytopenia with bacterial infections, bone pain, lymphadenopathy, hepatosplenomegaly, and sometimes spread to the central nervous system. It is subclassified on the basis of the surface antigens expressed, e.g., B-cell type, T-cell type. acute myelogenous leukemia acute myelogenous leukemia symptoms including anemia, fatigue, weight loss, easy bruising, thrombocytopenia, and granulocytopenia. Chronic leukemia leukemia in which the involved cell line is well leukemia in which the involved cell line is well differentiated, usually B lymphocytes, but immunologically incompetent. The main diseases in this group are chronic myelogenous leukemia, erythremia, chronic monocytic leukemia. They, in turn, are divided into forms with close clinical manifestations and pathogenesis. The main diseases in this group are chronic myelogenous leukemia, erythremia, chronic monocytic leukemia. They, in turn, are divided into forms with close clinical manifestations and pathogenesis. Hemorrhagic diathesis An increased susceptibility to bleeding due to a coagulation defect, which can be genetic or acquire. An increased susceptibility to bleeding due to a coagulation defect, which can be genetic or acquire. Iron deficiency anaemia Iron deficiency anaemia is a condition in which the body has too little iron in the bloodstream. This form of anaemia is more common in adolescents and in women before menopause. Blood loss from heavy periods, internal bleeding from the gastrointestinal tract, or donating too much blood can all contribute to this disease. Other causes can be from poor dietary habits or from chronic intestinal diseases. The signs and symptoms of this disease are: 1. Paleness 2. Headache 3. Irritability Symptoms of more severe iron deficiency anaemia include: 1. Dyspnea 2. Rapid heartbeat 3. Brittle hair and nails Many infants with iron deficiency don't show any symptoms early because the body's stored iron is depleted slowly. Folic Acid Deficiency Anaemia This form of anaemia is characterised by a lack of folic acid, one of the B group of vitamins, in the bloodstream. This is usually caused by an inadequate intake of folic acid, usually found in vegetables or by the overcooking of the vegetables. Alcoholism can also be a contributing factor in this form of anaemia. During pregnancy when the folic acid is used more or in infancy, this disease can also manifest itself. It can also be caused as a side effect of other blood disorders. Symptoms of the disorder include: 1. Weakness 2. Fatigue 3. Memory lapses 4. Irritability This condition can be avoided by including foods with folic acid in the diet. Such foods include beef liver, asparagus, and red beans. Pernicious anaemia Pernicious anaemia usually affects people between the ages of 50 and 60 and is a result of a lack of vitamin B12. The disease can be hereditary but some forms of the condition can be autoimmune diseases. People who have any autoimmune diseases are more likely to contract pernicious anaemia. Symptoms of this form of anaemia may include: 1. Fatigue 2. Dyspnea 3. Heart palpitations 4. Numbness or tingling in extremities Aplastic anaemia Aplastic anaemia is caused by an absence or reduction of red blood cells. This can happen through injury where the blood forming tissue in the bone marrow is destroyed. Because of this, the sufferer is unable to fight infection and is likely to be a heavy bleeder. Symptoms include: 1. Lethargy 2. Paleness 3. Purpura 4. Bleeding 5. Rapid heartbeat 6. Infections 7. Congestive heart failure There is no definite known cause for aplastic anaemia but it is thought to be caused by exposure to certain toxins and also to the hepatitis virus. Sickle Cell Anaemia This form of anaemia is of a hereditary nature and is a result of an abnormal type of red blood cells. Sickle cell anaemia is a life threatening disease and there is no prevention. Symptoms of this condition include: 1. Painful attacks in arms, legs and stomach 2. Jaundice in whites of the eyes 3. Fever 4. Chronic fatigue 5. Rapid heartbeat 6. Paleness Complications include leg ulcers, shock, cerebral hemorrhage, and orthopedic disorders. Polycythemia Vera This disease is more common in middle aged men and is characterised by an increase in red blood cells, leucocytes, and thrombocytes. There is a very fast and intense reproduction of cells and the bone marrow cells mature more rapidly than usual. The cause of this condition is unknown. Symptoms are: 1. Purplish coloured skin 2. Bloodshot eyes 3. Headache 4. Dizziness 5. Enlarged spleen Although the signs and symptoms of anaemia may seem overwhelming, the good news is that most forms can be effectively controlled with medication and dietary changes. Thrombus formation at the site of the damaged vascular wall A model of blood coagulation Bleeding disorders are a group of conditions that result when the blood cannot clot properly. In normal clotting, platelets stick together and form a plug at the site of an injured blood vessel. Proteins in the blood called clotting factors then interact to form a fibrin clot, which holds the platelets in place and allows healing to occur at the site of the injury while preventing blood from escaping the blood vessel. While too much clotting can lead to heart attack and stroke, the inability to form clots can be very dangerous as well, as it can result in excessive bleeding. Hemophilia is perhaps the most well-known bleeding disorder, although it is relatively rare. It affects mostly males. Many more people are affected by von Willebrand disease, the most common bleeding disorder in America. Von Willebrand disease can affect both males and females. Hemophiliavon Willebrand disease Bleeding disorders such as hemophilia and von Willebrand disease result when the blood lacks certain clotting factors. These diseases are almost always inherited, although in rare cases they can develop later in life if the body forms antibodies that fight against the blood's natural clotting factors. Individuals and pregnant women with a family history of bleeding disorders should talk to their doctors about detection and treatment. Symptoms of bleeding disorders may include: Easy bruising Bleeding gums Heavy bleeding from small cuts or dental work Unexplained nosebleeds Heavy menstrual bleeding FIBRINOLYTIC INHIBITORS: AMINOCAPROIC ACID Clinical uses of aminocaproic acid are as adjunctive therapy in hemophilia, as therapy for bleeding from fibrinolytic therapy, and as prophylaxis for rebleeding from intracranial aneurysms. FIBRINOLYTIC INHIBITORS: AMINOCAPROIC ACID Aminocaproic acid (EACA), which is chemically similar to the amino acid lysine, is a synthetic inhibitor of fibrinolysis. It competitively inhibits plasminogen activation. It is rapidly absorbed orally and is cleared from the body by the kidney. The usual oral dosage of EACA is 6 g four times a day. When the drug is administered intravenously, a 5 g loading dose should be infused over 30 minutes to avoid hypotension. Aminocaproic acid (EACA), which is chemically similar to the amino acid lysine, is a synthetic inhibitor of fibrinolysis. It competitively inhibits plasminogen activation. It is rapidly absorbed orally and is cleared from the body by the kidney. The usual oral dosage of EACA is 6 g four times a day. When the drug is administered intravenously, a 5 g loading dose should be infused over 30 minutes to avoid hypotension. Tranexamic acid is an analog of aminocaproic acid and has the same properties. It is administered orally with a 15 mg/kg loading dose followed by 30 mg/kg every 6 hours, but the drug is not currently available in the USA. Tranexamic acid is an analog of aminocaproic acid and has the same properties. It is administered orally with a 15 mg/kg loading dose followed by 30 mg/kg every 6 hours, but the drug is not currently available in the USA. ANTICOAGULANT DRUGS The ideal anticoagulant drug would prevent pathologic thrombosis and limit reperfusion injury, yet allow a normal response to vascular injury and limit bleeding. Theoretically this could be accomplished by preservation of the TF-VIIa initiation phase of the clotting mechanism with attenuation of the secondary intrinsic pathway propagation phase of clot development. At this time such a drug does not exist; all anticoagulants and fibrinolytic drugs have an increased bleeding risk as their principle toxicity Coumarin anticoagulants Administration & Dosage Treatment with warfarin should be initiated with standard doses of 5-10 mg rather than the large loading doses formerly used. The initial adjustment of the prothrombin time takes about 1 week, which usually results in a maintenance dose of 5-7 mg/d. The prothrombin time (PT) should be increased to a level representing a reduction of prothrombin activity to 25% of normal and maintained there for long-term therapy. When the activity is less than 20%, the warfarin dosage should be reduced or omitted until the activity rises above 20%. Schematic representation of the fibrinolytic system Fibrinolytic drugs Streptokinase Streptokinase Anistreplase Anistreplase alteplase alteplase Reteplase Reteplase Tenecteplase Tenecteplase ANTIPLATELET AGENTS several targets for platelet inhibitory drugs have been identified: Inhibition of prostaglandin synthesis Inhibition of prostaglandin synthesisASPIRIN Inhibition of ADP-induced platelet aggregation CLOPIDOGREL & TICLOPIDINE Inhibition of ADP-induced platelet aggregation CLOPIDOGREL & TICLOPIDINE BLOCKADE OF PLATELET GLYCOPROTEIN IIB/IIIA RECEPTORS (Abciximab, Eptifibatide, Tirofiban ) BLOCKADE OF PLATELET GLYCOPROTEIN IIB/IIIA RECEPTORS (Abciximab, Eptifibatide, Tirofiban ) ADDITIONAL ANTIPLATELET-DIRECTED DRUGS (Dipyridamole, Cilostazol ) ADDITIONAL ANTIPLATELET-DIRECTED DRUGS (Dipyridamole, Cilostazol ) Absorption, transport, and storage of iron The average diet contains mg of elemental iron daily. A normal individual absorbs 5-10% of this iron, or about mg daily. Iron is normally absorbed in the duodenum and proximal jejunum, although the more distal small intestine can absorb iron if necessary. Iron absorption increases in response to low iron stores or increased iron requirements. Total iron absorption increases to 1-2 mg/d in normal menstruating women and may be as high as 3-4 mg/d in pregnant women. Enzymatic reactions that use vitamin B12, folates Vitamin B12 serves as a cofactor for several essential biochemical reactions in humans. Deficiency of vitamin B12 leads to anemia, gastrointestinal symptoms, and neurologic abnormalities.