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==

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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)

• 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)

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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)

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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

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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)

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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%%

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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

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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

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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

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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

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→ Coagulopathy

• Has 2 mechanisms

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  1. Platelet issue (dysfunction)
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  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

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==→ 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

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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

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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

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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

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• 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

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