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Hematology & Anemias

Blood Review

  • Blood is a connective tissue

  • The blood is: 55% plasma, 45% formed elements (44% RBCs)

Blood Tests

  • H & H: Hemoglobin and hematocrit, used for anemia testing

    • Hematocrit: % of any RBCs in any volume of blood (max is 44%)

  • CBC: Complete blood test; measures hemoglobin, hematocrit, platelet and WBC count, used for infection

    • ALWAYS ordered with a differential

Anemia Definition

“Inability of the blood to supply the tissues with adequate oxygen for proper metabolic function”

  • Either inadequate hemoglobin or RBC can lead to anemia

  • Hg: hemoglobin concentration

  • Hct: hematocrit concentration (packed cell volume)

  • RBC: red blood cell count

  • ANEMIA IS NOT A DISEASE; expression of an UNDERLYING disorder/disease

→ Normal Hg and Hct Levels

  • Hg < 13 in men; Hct <41%

  • Hg < 12 in women; Hct <36%

  • Hg <14 in men; Hg <12 in women (with malignancy)

Men

Women

Hemoglobin (Hb)

13.2-16.7

11.9-15.0

Hematocrit (Hct)

38-48%

35-44%

Red Cell Count

4.2-5.6

3.8-5.0

Reticulocyte Count

0.5-1.5

0.5-1.5

Mean Cell Volume (MCV)

81-97

81-97

  • Lastly, the anemia morphology:

    • Size: Macrocytic, microcytic, normocytic

      • Macro= the entire RBC

      • Micro= hemoglobin only

    • Hemoglobin content: Normochromic and hypochromic

  • Microcytic, MCV < 80 (reduced iron availability)

  • Normocytic, 80 < MCV < 100

  • Macrocytic, MCV > 100 (liver disease/B12 deficiency)

Lab Values

  • Hematocrit: volume of packed RBCs per unit of blood, expressed as a % (ex: 44% is the max)

    • 38-44% is in normal range

  • Reticulocyte: young RBC, not functionally mature, anemia due to hemolysis or bleeding is characterized by reticulocytosis

    • Normal value: ~1%

    • Increase in reticulocytes is due to compensation to bring up the RBC

  • Mean corpuscular volume (MCV): reflect average size or volume of RBC, will tell if the patient is micro, macro, or normcytic

  • Mean cell hemoglobin concentration (MCHC): indicates the concentration of Hb in the average RBC, or the ratio of the weight of the Hb to the volume in which it is contained (chromicity/color)

Symptoms of Anemia

  • Easy fatigue and loss of energy

  • Tachycardia, rapid heart rate

  • Shortness of breath

  • Headache

  • Difficulty concentrating

  • Dizziness

  • Pale skin

  • Leg cramps

  • Insomnia

Macrocytic Normochromic Anemia

Characterized by unusually large stem cells

  • Can also be termed megaloblastic anemias

→ PATHOGENESIS:

  • Defective DNA synthesis in rapidly dividing cells

    • Caused by B12 or folate deficiencies

  1. Vitamin B12 deficiency:

    • Is B12 deficiency due to lack of intrinsic factor OR, normal intrinsic factor level, but not enough B12 absorption?

    • Autoimmune causes = pernicious anemia

    • Non-autoimmune causes = dietary, gastric bypass, tapeworm, pancreatic insufficiency

  2. Folate deficiency: dietary or pregnancy causes

  3. Other causes: alcohol use, drugs, malabsorption

Folate vs. B12 = The only difference is there are no neuro symptoms in folate deficiency

Pernicious Anemia

Macrocytic normochromic anemia

  • Caused by autoimmune disorder to attack against parietal cells

  • Lack of intrinsic factors

    • Intrinsic factor needed for B12 absorption → B12 deficiency

  • S&S: Neurological

    • Paresthesia, pins and needles in hands or feet

    • Lost sense of touch

    • Wobbly gait or trouble walking

    • Clumsiness and stiffness of the arms and legs

    • Dementia → long term impact

  • Diagnosis:

    • Antibodies against parietal cells

Folate Deficiency Anemia

Macrocytic normochromic

  • Dietary intake related

  • Impacts rapidly dividing cells

  • Absorption of folate occurs in upper small intestine

  • Not dependent on any other factors

  • S&S:

    • Neuro symptoms not seen

    • Cheilosis, scales and fissures of the mouth

    • Stomatitis, painful ulcers of buccal mucosa and tongue

  • Diagnosis:

    • Methylmalonic acid and homocysteine level (B12 vs. folate deficiency)

Microcytic Hypochromic

Characterized by RBCs that are abnormally small and contain reduced amounts of hemoglobin; IRON DEFICIENCY

  • Disorders of iron metabolism, pophyrin and heme synthesis, and globin synthesis

  • Etiology:

    • Iron deficiency is the most commonly seen

    • Thalassemia is rare

    • Sideroblastic anemia is also rare

    • Anemia of chronic disease

Iron Deficiency Anemia

Microcytic hypochromic

→ PATHOGENESIS:

  • Chronic blood loss, #1 common cause (pathologic vs. physiologic)

    • Menstruation (physiologic)

    • Occult blood loss (cannot see where blood loss is coming from, pathologic)

    • Malignancy (blood loss that you can see, pathologic)

  • Inadequate iron absorption (nutritional deficiency)

    • Diet low in heme iron (fish + meat)

    • Gastrointestinal disease or surgery (small intestine)

    • Excessive cow’s milk intake in infants (prevents iron absorption)

    • Pregnancy (physiologic demand increased)

  • Malabsorption

  • S&S: Impacts more of the epithelial

    • Symptoms of anemia plus;

    • Glossitis, smooth tongue

    • Restless legs

    • Angular stomatitis, cracking corners of the mouth

    • Koilonychia, thin brittle spoon-shaped fingernails

  • Tests for Iron Deficiency:

    • Hgb: ⬇️

    • Hct: ⬇️

    • MCV: ⬇️

    • Serrum ferritin: ⬇️

    • Serum iron/transferrin: ⬇️

    • Peripheral blood smear

    • Bone marrow iron stain (invasive and painful)

  • TREATMENT:

    • Oral iron salts; ferrous sulfate 325 mg po Q day (given to pregnant women)

    • Vitamin C can facilitate iron absorption or orange juice would suffice

    • DO NOT TRANSFUSE, UNLESS SEVERE (<6.5g/dl), considered aggressive form of treatment; will mask the issue

Normocytic Anemia

Acute blood loss

→ ETIOLOGY:

  • Hemolysis: sickle cell disease (appears in waves, not constant, 4-6 years can sickle), immune system, transfusion rejection (mismatched blood type)

  • Bone marrow suppression = myeloma

  • Anemia of chronic disease = chronic kidney disease

  • Hypothyroidism = slower production of RBCs

Anemia of Chronic Disease

Normocytic anemia → microcytic hypochromic

  • Aka, anemia of inflammation

  • Decreased erythropoiesis (low erythropoietin)

    • Impaired iron utilization

  • INITIALLY normocytic-normochromic, but becomes microcytic-hypochromic

  • Treatment is aimed at an underlying disorder

    • Results from:

      • Decreased erythrocyte life span

      • Suppressed production of erythropoietin

      • Ineffective bone marrow response

      • Altered iron metabolism in macrophages

        • Lead to anemia of chronic disease

Platelet Dysfunction & Coagulopathy

  • Hemorrhage: extraversion of blood from vessels

  • Hematoma: external or accumulation within a tissue

    • Benign (bruise) to fatal (retroperitoneal hematoma)

    • Jaundice

    • Large blood into cavities

  • Petechia, minute (1-2mm in diameter)

  • Purpura >3mm <1cm

  • Ecchymoses 1-2cm

→ Coagulopathy

  • Has 2 mechanisms

      1. Platelet issue (dysfunction)

      1. Coagulation cascade

→ Platelet Issue/Dysfunction

  • Increased bleeding time in presence of normal platelet counts

  • Disorders can be congential or acquired

  • TESTING FOR PLATELET DYSFUNCTION:

    • Order a coagulation panel

      • PT → Goes with PTT

      • PTT → Goes with PT, tests for the intrinsic or extrinsic pathways or the clotting factors

      • INR → Anticoagulate in the US that is universally understood to not withdraw care by external physicians in the states or overseas

→ COAGULATION PATHWAY DYSFUNCTIONS

  • Vitamin K deficiency, Hemophilia, DIC

  • Intrinsic, extrinsic, and common pathways

von Willebrand Disease (Platelet Dysfunction)

  • Autosomal dominant disorder

  • MOST COMMON inherited bleeding disorder

  • vWF facilitates platelet adhesion → causes mild or moderate bleeding

  • Defective platelet adherence PFA-100 test

Vitamin K Deficiency (Coagulation Pathway Dysfunction)

→ Vitamin K deficiency (factors 2,7,9,10)

  • Necessary for synthesis and regulation of prothrombin (2), the procoagulant factors (7,9,10) and proteins C and S (anticoagulants)

  • Newborn/premature infants → liver not mature, get shot of vitamin K in bum right after birth

  • Poor intake → seen in homeless population and in addicts

  • Liver disease → seen with in combination with poor intake

  • Defective absorption:

    • Generalized malabsorption → Crohns and Celiacs Disease

    • Biliary disease

→ PATIENT RISK:

  • Diminished production by bacteria in gut (antibiotic treatment)

  • Vitamin K antagonists

    • Warfarin (Coumadin) → blood thinner, cannot eat vitamin K rich foods or else it will counteract the treatment

  • Heparin

  • Certain antibiotics

Hemophilia (Coagulation Pathway Dysfunction)

  • Inherited deficiency of factor 8 (hemophilia A) or factor 9 (hemophilia B) or factor 10 (hemophilia C)

  • Sex linked inheritance, almost all patients are males

  • Female carriers may have mild symptoms

  • Most bleeding into joints, muscles, mucosal and CNS bleeding uncommon

Disseminated Intravascular Coagulation (Coagulation Pathway Dysfunction)

  • DIC

  • Develops RAPIDLY

  • Acquired disorder in which clotting and hemorrhage simultaneously occur

  • Endothelial damage/tissue factor is the primary initiator of DIC

→ PATHOPHYSIOLOGY:

  • Increased protease activity in the blood caused by unregulated release of thrombin with subsequent fibrin formation and accelerated fibrinolysis

  • Consumptive coagulopathy → uncontrolled hemostasis, patient bleeds out

→ ETIOLOGY:

  • High mortality rate

  • Infection by gram negative bacteria is the MOST COMMON CAUSE

  • Carcinomas/leukemias

  • Trauma, pregnancy (amniotic fluid gets into mother’s blood stream), transfusion reaction

  • Clinical signs and symptoms demonstrate wide variability:

    • Bleeding from venipuncture sites

    • Bleeding from arterial lines

    • Purpura, petechiae, and hemotomas

    • Symmetric cyanosis of the fingers and toes

B

Hematology & Anemias

Blood Review

  • Blood is a connective tissue

  • The blood is: 55% plasma, 45% formed elements (44% RBCs)

Blood Tests

  • H & H: Hemoglobin and hematocrit, used for anemia testing

    • Hematocrit: % of any RBCs in any volume of blood (max is 44%)

  • CBC: Complete blood test; measures hemoglobin, hematocrit, platelet and WBC count, used for infection

    • ALWAYS ordered with a differential

Anemia Definition

“Inability of the blood to supply the tissues with adequate oxygen for proper metabolic function”

  • Either inadequate hemoglobin or RBC can lead to anemia

  • Hg: hemoglobin concentration

  • Hct: hematocrit concentration (packed cell volume)

  • RBC: red blood cell count

  • ANEMIA IS NOT A DISEASE; expression of an UNDERLYING disorder/disease

→ Normal Hg and Hct Levels

  • Hg < 13 in men; Hct <41%

  • Hg < 12 in women; Hct <36%

  • Hg <14 in men; Hg <12 in women (with malignancy)

Men

Women

Hemoglobin (Hb)

13.2-16.7

11.9-15.0

Hematocrit (Hct)

38-48%

35-44%

Red Cell Count

4.2-5.6

3.8-5.0

Reticulocyte Count

0.5-1.5

0.5-1.5

Mean Cell Volume (MCV)

81-97

81-97

  • Lastly, the anemia morphology:

    • Size: Macrocytic, microcytic, normocytic

      • Macro= the entire RBC

      • Micro= hemoglobin only

    • Hemoglobin content: Normochromic and hypochromic

  • Microcytic, MCV < 80 (reduced iron availability)

  • Normocytic, 80 < MCV < 100

  • Macrocytic, MCV > 100 (liver disease/B12 deficiency)

Lab Values

  • Hematocrit: volume of packed RBCs per unit of blood, expressed as a % (ex: 44% is the max)

    • 38-44% is in normal range

  • Reticulocyte: young RBC, not functionally mature, anemia due to hemolysis or bleeding is characterized by reticulocytosis

    • Normal value: ~1%

    • Increase in reticulocytes is due to compensation to bring up the RBC

  • Mean corpuscular volume (MCV): reflect average size or volume of RBC, will tell if the patient is micro, macro, or normcytic

  • Mean cell hemoglobin concentration (MCHC): indicates the concentration of Hb in the average RBC, or the ratio of the weight of the Hb to the volume in which it is contained (chromicity/color)

Symptoms of Anemia

  • Easy fatigue and loss of energy

  • Tachycardia, rapid heart rate

  • Shortness of breath

  • Headache

  • Difficulty concentrating

  • Dizziness

  • Pale skin

  • Leg cramps

  • Insomnia

Macrocytic Normochromic Anemia

Characterized by unusually large stem cells

  • Can also be termed megaloblastic anemias

→ PATHOGENESIS:

  • Defective DNA synthesis in rapidly dividing cells

    • Caused by B12 or folate deficiencies

  1. Vitamin B12 deficiency:

    • Is B12 deficiency due to lack of intrinsic factor OR, normal intrinsic factor level, but not enough B12 absorption?

    • Autoimmune causes = pernicious anemia

    • Non-autoimmune causes = dietary, gastric bypass, tapeworm, pancreatic insufficiency

  2. Folate deficiency: dietary or pregnancy causes

  3. Other causes: alcohol use, drugs, malabsorption

Folate vs. B12 = The only difference is there are no neuro symptoms in folate deficiency

Pernicious Anemia

Macrocytic normochromic anemia

  • Caused by autoimmune disorder to attack against parietal cells

  • Lack of intrinsic factors

    • Intrinsic factor needed for B12 absorption → B12 deficiency

  • S&S: Neurological

    • Paresthesia, pins and needles in hands or feet

    • Lost sense of touch

    • Wobbly gait or trouble walking

    • Clumsiness and stiffness of the arms and legs

    • Dementia → long term impact

  • Diagnosis:

    • Antibodies against parietal cells

Folate Deficiency Anemia

Macrocytic normochromic

  • Dietary intake related

  • Impacts rapidly dividing cells

  • Absorption of folate occurs in upper small intestine

  • Not dependent on any other factors

  • S&S:

    • Neuro symptoms not seen

    • Cheilosis, scales and fissures of the mouth

    • Stomatitis, painful ulcers of buccal mucosa and tongue

  • Diagnosis:

    • Methylmalonic acid and homocysteine level (B12 vs. folate deficiency)

Microcytic Hypochromic

Characterized by RBCs that are abnormally small and contain reduced amounts of hemoglobin; IRON DEFICIENCY

  • Disorders of iron metabolism, pophyrin and heme synthesis, and globin synthesis

  • Etiology:

    • Iron deficiency is the most commonly seen

    • Thalassemia is rare

    • Sideroblastic anemia is also rare

    • Anemia of chronic disease

Iron Deficiency Anemia

Microcytic hypochromic

→ PATHOGENESIS:

  • Chronic blood loss, #1 common cause (pathologic vs. physiologic)

    • Menstruation (physiologic)

    • Occult blood loss (cannot see where blood loss is coming from, pathologic)

    • Malignancy (blood loss that you can see, pathologic)

  • Inadequate iron absorption (nutritional deficiency)

    • Diet low in heme iron (fish + meat)

    • Gastrointestinal disease or surgery (small intestine)

    • Excessive cow’s milk intake in infants (prevents iron absorption)

    • Pregnancy (physiologic demand increased)

  • Malabsorption

  • S&S: Impacts more of the epithelial

    • Symptoms of anemia plus;

    • Glossitis, smooth tongue

    • Restless legs

    • Angular stomatitis, cracking corners of the mouth

    • Koilonychia, thin brittle spoon-shaped fingernails

  • Tests for Iron Deficiency:

    • Hgb: ⬇️

    • Hct: ⬇️

    • MCV: ⬇️

    • Serrum ferritin: ⬇️

    • Serum iron/transferrin: ⬇️

    • Peripheral blood smear

    • Bone marrow iron stain (invasive and painful)

  • TREATMENT:

    • Oral iron salts; ferrous sulfate 325 mg po Q day (given to pregnant women)

    • Vitamin C can facilitate iron absorption or orange juice would suffice

    • DO NOT TRANSFUSE, UNLESS SEVERE (<6.5g/dl), considered aggressive form of treatment; will mask the issue

Normocytic Anemia

Acute blood loss

→ ETIOLOGY:

  • Hemolysis: sickle cell disease (appears in waves, not constant, 4-6 years can sickle), immune system, transfusion rejection (mismatched blood type)

  • Bone marrow suppression = myeloma

  • Anemia of chronic disease = chronic kidney disease

  • Hypothyroidism = slower production of RBCs

Anemia of Chronic Disease

Normocytic anemia → microcytic hypochromic

  • Aka, anemia of inflammation

  • Decreased erythropoiesis (low erythropoietin)

    • Impaired iron utilization

  • INITIALLY normocytic-normochromic, but becomes microcytic-hypochromic

  • Treatment is aimed at an underlying disorder

    • Results from:

      • Decreased erythrocyte life span

      • Suppressed production of erythropoietin

      • Ineffective bone marrow response

      • Altered iron metabolism in macrophages

        • Lead to anemia of chronic disease

Platelet Dysfunction & Coagulopathy

  • Hemorrhage: extraversion of blood from vessels

  • Hematoma: external or accumulation within a tissue

    • Benign (bruise) to fatal (retroperitoneal hematoma)

    • Jaundice

    • Large blood into cavities

  • Petechia, minute (1-2mm in diameter)

  • Purpura >3mm <1cm

  • Ecchymoses 1-2cm

→ Coagulopathy

  • Has 2 mechanisms

      1. Platelet issue (dysfunction)

      1. Coagulation cascade

→ Platelet Issue/Dysfunction

  • Increased bleeding time in presence of normal platelet counts

  • Disorders can be congential or acquired

  • TESTING FOR PLATELET DYSFUNCTION:

    • Order a coagulation panel

      • PT → Goes with PTT

      • PTT → Goes with PT, tests for the intrinsic or extrinsic pathways or the clotting factors

      • INR → Anticoagulate in the US that is universally understood to not withdraw care by external physicians in the states or overseas

→ COAGULATION PATHWAY DYSFUNCTIONS

  • Vitamin K deficiency, Hemophilia, DIC

  • Intrinsic, extrinsic, and common pathways

von Willebrand Disease (Platelet Dysfunction)

  • Autosomal dominant disorder

  • MOST COMMON inherited bleeding disorder

  • vWF facilitates platelet adhesion → causes mild or moderate bleeding

  • Defective platelet adherence PFA-100 test

Vitamin K Deficiency (Coagulation Pathway Dysfunction)

→ Vitamin K deficiency (factors 2,7,9,10)

  • Necessary for synthesis and regulation of prothrombin (2), the procoagulant factors (7,9,10) and proteins C and S (anticoagulants)

  • Newborn/premature infants → liver not mature, get shot of vitamin K in bum right after birth

  • Poor intake → seen in homeless population and in addicts

  • Liver disease → seen with in combination with poor intake

  • Defective absorption:

    • Generalized malabsorption → Crohns and Celiacs Disease

    • Biliary disease

→ PATIENT RISK:

  • Diminished production by bacteria in gut (antibiotic treatment)

  • Vitamin K antagonists

    • Warfarin (Coumadin) → blood thinner, cannot eat vitamin K rich foods or else it will counteract the treatment

  • Heparin

  • Certain antibiotics

Hemophilia (Coagulation Pathway Dysfunction)

  • Inherited deficiency of factor 8 (hemophilia A) or factor 9 (hemophilia B) or factor 10 (hemophilia C)

  • Sex linked inheritance, almost all patients are males

  • Female carriers may have mild symptoms

  • Most bleeding into joints, muscles, mucosal and CNS bleeding uncommon

Disseminated Intravascular Coagulation (Coagulation Pathway Dysfunction)

  • DIC

  • Develops RAPIDLY

  • Acquired disorder in which clotting and hemorrhage simultaneously occur

  • Endothelial damage/tissue factor is the primary initiator of DIC

→ PATHOPHYSIOLOGY:

  • Increased protease activity in the blood caused by unregulated release of thrombin with subsequent fibrin formation and accelerated fibrinolysis

  • Consumptive coagulopathy → uncontrolled hemostasis, patient bleeds out

→ ETIOLOGY:

  • High mortality rate

  • Infection by gram negative bacteria is the MOST COMMON CAUSE

  • Carcinomas/leukemias

  • Trauma, pregnancy (amniotic fluid gets into mother’s blood stream), transfusion reaction

  • Clinical signs and symptoms demonstrate wide variability:

    • Bleeding from venipuncture sites

    • Bleeding from arterial lines

    • Purpura, petechiae, and hemotomas

    • Symmetric cyanosis of the fingers and toes