Pharmacology

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Pharmacology 3.2

1 Sem/A.Y. 2015-2016

Hematinics, Hemostatics and Coagulants Glenn V. Guevara, MD B. Erythropoiesis

OUTLINE A. B. C. D. E. F. G. H. I.

September 11, 2015

Introduction Anemia Iron Deficiency Anemia Hypoproliferative Anemia Megaloblastic Anemia Myelopoiesis Megakaryopoiesis Hemostasis Summary

HEMATINICS, HEMOSTATICS AND COAGULANTS A. INTRODUCTION A. Hematopoiesis

Figure 2: Erythropoiesis 

Erythropoietin: main regulator of erythropoiesis o Stimulate hematopoietic stem cells from the bone marrow to form RBCs o Released by kidneys in response to low O2 tension o Factors that decrease tissue oxygenation: low blood pressure, anemia, low hemoglobin, poor blood flow, pulmonary disease o Increased number of RBCs results to an increased O2 carrying capacity, inducing a negative feedback on EPO

Figure 3: Erythropoietin stimulation and inhibition  Figure 1: Hematopoiesis 

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Formation of blood components o Erythropoiesis: formation of RBCs o Myelopoiesis: formation of granulocytes and monocytes o Megakaryopoiesis: formation of platelets Derived from hematopoietic stem cells

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Iron: needed for maturation of red blood cells o Each RBC contains several hundred hemoglobin molecules which transport oxygen o Iron is needed for the production of heme Cobalamin Folic Acid B. ANEMIA Decrease in the amount of RBCs or hemoglobin in the blood Leads to lowered ability of blood to carry oxygen

Causes: o Blood loss (most common cause): trauma, GI bleeding, abnormal menstrual bleeding o Decreased RBC production  Nutrient deficiency (iron, cobalamin, folic acid); most common cause among decreased RBC production

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Thalessemia Bone marrow cancers Kidney disease Chronic infections Fluid overload- decrease in RBC production due to volume expansion  Increased RBC breakdown- Sickle Cell Disease

Hematocrit (Hct) Male Female

Male Female

Hgb Count 13.8 to 18.0 g/dl (8.56-11.17 mmol/L) 12.1 to 15.1 g/dl (7.51-9.37 mmol/L) 11-16 g/dL (6.83-9.93 mmol/L) 11-14 g/dL (6.83-9.93 mmol/L) RBC Count 4.7-6.1 millions/uL 4.2-5.4 millions/uL

MCV

80-100 fl (femtoliters)

Male

Types of Anemia o By size: normocytic, macrocytic, microcytic o By color: normochromic, hypochromic, hyperchromic

Female Children Pregnant

Signs and Symptoms

45 % 40 %

MCH 27-31 pg/cell (picograms) MCHC 32-36 g/dL or 19.9-22.3 mmol/L Table 1: Normal values for CBC C. IRON DEFICIENCY ANEMIA  Most common cause of anemia  Due to increased iron demand, iron loss or decreased iron intake  More common in females (so take care and love your mom, sisters, daughters and girlfriends, boys.  There are a lot of illnesses associated with women.)

 Microcytic and hypochromic

Figure 4: Shows a somewhat good looking man with a creepy gaze. Also shown are the General Signs and Symptoms of Anemia. Diagnostic Tests o Hemoglobin Count – hemoglobin concentration o Hematocrit - proportion of blood volume occupied by RBC; also called "packed cell volume" or "erythrocyte volume fraction" (about 3x the Hgb concentration) o RBC Count – number of RBC o Mean Corpuscular Volume (MCV)  Average volume or size of RBC  MCV = (Hct x 10) / RBC number in million  Normal MCV and decreased Hgb/Hct = normocytic anemia; low MCV = microcytic and vice versa o Mean Corpuscular Hemoglobin (MCH)  Average mass of hemoglobin per RBC in a sample of blood  Assess COLOR of the ANEMIA  MCH = (Hgb x 10) / RBC number in million o Mean Corpuscular Hemoglobin Concentration (MCHC)  Concentration of hemoglobin in a volume of packed RBC – the HUE OF RBC  MCHC = MCH/MCV x 100  This is more sensitive for measuring the actual color because it considers both MCV and MCH o Blood Smear – morphology of RBCs

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Causes:  Increased demand o Growth and development – children, adolescents o Pregnancy  Blood loss o Parasitic infections o Menorrhagia o Peptic ulcers o Patients on anticoagulants (aspirin, clopidogrel, etc)  Decreased intake o Low iron diet: vegetarians, vegans  o Malabsorption: intestinal resection, celiac disease, inflammatory bowel disease, decreased acidity of stomach (due to prolonged proton pump inhibitor use, e.g. omeprazole) A.

Diagnostic Tests (Why do we need to know this? Kinda boring but just see yourself as House, Shepherd, Yang or Grey diagnosing your anemia patient. Wee!)

CBC (see diagnostic tests of anemia) Serum iron  It is the amount of circulating iron bound to transferrin  It can increase immediately on initiation of Fe supplementation Serum ferritin  Most SENSITIVE indicator but is not reliable if within normal limits  Remember that ferritin is the storage form of iron

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Pharmacology 3.02 Total Iron Binding Capacity (TIBC)  Most SPECIFIC indicator (when levels are high)  It measures the blood capacity to bind iron with transferrin. It is an indirect measure of transferrin  Transferrin is the transporter of iron in the blood. An increase would point to an increased need for iron (2017B)  It is usually elevated in IDA Transferrin Saturation Index (Percent Saturation/ Iron Saturation)  It is the percent saturation or iron saturation of transferrin  How much iron is currently bound to transferrin (2017B)  SI/TIBC x100 Table 2: Normal values Serum Iron Male 65-176 μg/dL Female 50-170 μg/dL Children 50-120 μg/dL Newborn 100-250 μg/dL Serum Ferritin Male 18-270 ng/mL Female 18-160 ng/mL Children 7-140 ng/mL Newborn 25-200 ng/mL Total Iron Binding Capacity 240-450 μg/dL Transferrin Saturation Index Male >15-50% Female >12-50% Still Possible 5-10% Definitely Abnormal