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)

• 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)
    * $38-44$
• ==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)
    * \
  
      2. 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