Hematology 3a

polycythemia

excess RBC in circulation

anemia

• reduction in the total number of erythrocytes (RBC’s) in circulating blood

• decrease in quantity or quality of HB

• this results in decrease O2 carrying capacity of the blood → hypoxemia → hypoxia

causes of anemia

• impaired erythrocyte production

• blood loss (acute/chronic)

• increased erythrocyte destruction

mild signs of anemia

• fatigue/ weakness/ dizziness

• pallor (skin and mucus membranes)

• smooth tongue

  • beefy tongue aka glossitis (B12 def)

• cold hands and feet

• nail changes

• hair loss

• may only cause s/s during exertion

dangerous signs of anemia

• SOB/ dyspnea

• chest pain/ arrhythmias/ tachycardia

• orthostatic hypotension or syncope

• neuro s/s (B12 def

Mean Cell Volume (MCV)

• average volume of RBC

• determines if microcytic, normocytic, or macrocytic

Mean Cell Hemoglobin (MCH)

• color

• average mass of HB per RBC

• bigger RBC will have more Hb

Mean Cell Hemoglobin Concentration (MCHC)

• the average concentration of Hb in a given volume of packed RBC

• determines if RBC is hypochromic, normochromic, or hyperchromic

Red Cell Distribution Width (RDW)

• measure variation of RBC volume

• higher value = more variation in size 

Different RBC size/ volume

• normocytic

• microcytic

• macrocytic

Hemoglobin Concentration

• normochromic

• hypochromic

• hyperchromic

Loss of RBC’s

blood loss (acute or chronic)

Decreased or abnormal production of RBC’s

deficiency of raw materials (iron, folate/ B9, B12)

Increased destruction of RBC’s

hemolytic anemias (sickle cell, thalassemias, etc.)

Anemia of Acute blood loss

• bleeding

  • trauma, peptic ulcer, hemorrhoids, GI bleed

• Hct is low due to hemodilution

  • shift of fluid from the interstitial space to compensate for loss

• Normocytic, normochromic

  • decreased Hg, decreased Hct, normal MCV, normal MCHC

• production of erythropoietin by the kidneys 

Anemia of Chronic Blood Loss

• rate of loss exceeds ability to regenerate 

• microcytic hypochromic anemia 

  • decreased MCV, decreased MCH, decreased MCHC

• iron reserves become depleted so iron deficiency occurs

  • occult (no s/s) blood loss can take months to cause this

    • MCC in elderly: chronic GI bleed

    • MCC in adult females: menorrhagia (heavy menses)

Iron Deficiency Anemia

• decreased MCV - microcytic

• decreased MCHC - hypochromic

• most common worldwide

• very common in elderly due to GI bleeds

• two main etiologies

  • inadequate iron intake

  • chronic blood loss

Chronic blood loss

• chronic NSAID use (bleeding ulcers

• menorrhagia

• esophageal varcies

• PUD

• UC

• Crohn’s 

• GI cancers

• hemorrhoids

• parasitic infections

Inadequate Iron intake

• dietary lack

• lead poisoning → interferes with iron absorption 

• impaired absorption - celiac disease, chronic disease, low gastric, HCl

• increased requirements: growing infants children/adolescents, menstruating females, pregnant females

signs and symptoms of iron deficiency anemia

• gradual onset → onset does not appear until Hb is below 7 or 8 g/dl

• fatigue, tachycardia, palpitations, tachypnea

• Koilonychia, angular cheilitis/stomcititis, alopecia

• tongue → pale, shiny and smooth

• pica → eating disorder

  • craving and eating of non-nutritional substances

Diagnosis of Iron Deficiency Anemia

• decrease

  • RBC’s, Hb, Hct

  • Ferritin-stored iron

  • Fe

• increased

  • total iron-binding capacity (TIBC)

  • measures transferrin 

Macrocytic Normochromic Anemias aka Megaloblastic Anemias

• Increased MCV, increase MCH, normal MCHC

• megaloblasts in the bone marrow become unusually large erythrocytes

• bigger is NOT better 

  • bigger RBC’s die early to anemia

Causes of Macrocytic Normochromic Anemias

• B12 (Cobalamin) deficiency

• B9 (Folate) deficiency 

Risks of Macrocytic Normochromic Anemias

• increased levels of homocystenine are associated with inflammation

  • increased risk of MI and CVD

• functions of B12 and B9

  • formation of RBC’s

  • maintenance of myelin (B12)

    • neuro symptoms with B12 deficiency

  • DNA production

    • conservation of homocysteine to methionine

B12 Deficiency causes

• dietary deficiency/ vegetarian

• impaired GI absorption 

  • celiac disease, IBD

  • metformin side effect (Tx: Type II DM)

• intrinsic factor (IF) deficiency

  • called pernicious anemia

    • causes Type A Chronic Atrophic Gastritis

    • antibodies to parietal cells and IF

  • pernicious = fatal

  • IF is needed to absorb B12 at the illeum

  • gastric bypass surgery = decreased intrinsic factor

B9 deficiency cause

• dietary deficiency 

  • B9 found in beans, lentils, asparagus, leafy greens (spinach, collard greens, kale)

• alcoholics

• pregnancy

Cobalamin (B12) Deficiency Anemia

• s/s

  • of typical anemia

  • smooth and beefy red tongue

  • CNS symptoms due to nerve demyelination

    • paresthesias of fingers and feet (pins and needles)

    • difficulty walking

    • altered mental status

• Dx

  • blood: CBC, vitB12, IF, homocysteine

  • figure out underlying cause - gastric biopsy

• Tx:

  • vit 12 cobalamin

• Altered Mental status

  • mania

  • psychosis

  • memory impairment

  • irritability

  • depression

  • personality changes

Folate (Folic Acid) Deficiency Anemia

• a deficiency of folic acid results in megaloblastic anemia with the same characteristics as those of vit B12 deficiency

• no neurologic changes or beefy red tongue

• sources: beans, lentils, asparagus, leafy greens (spinach, collards, kale)

• Dx: CBC, folate, homocystenine

• Tx: dietary replacement

Sickle Cell Anemia

• genetic RBC disorders

• causes

  • genetic → autosomal recessive 

  • african american

  • HbS instead of HbA

  • sickle cell trait - 1 allele for HbS and 1 for HbA (production against malaria, no anemia)

Signs and symptoms of sickle cell anemia

• sickling of cells → abdominal and bone pain, ulcerations, thrombi infarcts 

• hemolytic crisis → jaundice and hematuria 

• splenic sequestration crisis 

• aplastic crisis (RBC’s live 10-20 days)

• lack oxygen and dehydration increase sickling

Testing for sickle cell

• CBC: decreased Hb, decreased Hct, decreased MCV, increased MCHC - microcytic hyperchromic anemia 

• Howell - jolly bodies

• hemoglobin electrophoresis HbS

Treatment for Sickle Cell Anemia

• antibiotics

• hydroxyurea (stimulates HbF)

Hemostasis

• the arrest of bleeding from a broken blood vessel

• capillary, venule, and arterioles ruptures are common 

  • easily fixed by our hemostatic mechanisms medium and large blood vessel ruptures

  • need external assistance to help our hemostatic mechanisms work

Steps of hemostasis

1. vasospasm → decreased blood loss

2. Platelet plug

• platelet activation (vWF)

• platelet aggregation (vWF)

• platelet degranulation

• clotting factors and many more substances

3. Coagulation Cascade

• extrinsic pathway (tissue factor)

• intrinsic pathway (factor XII)

• common pathway (factor X)

Von Willebrand Factor (vWF)

• released from platelets and damaged endothelial cells

• binds platelets to platelets 

  • aka: platelet aggregation

• binds platelets to the exposed sub endothelial collagen receptors 

  • aka platelet adhesion

Clotting Cascade

12 clotting facts are involved

• plasma proteins that are synthesized in the liver 

Intrinsic Pathway (aPTT)

• initiated by Factor XII coming into contact with exposed collagen

• slow

• factors VIII (hemophillia A) + IX (hemophillia B)

Extrinsic Pathway (PT)

• damaged tissue exposes and releases a sub-endothelial membrane protein called tissue factor 

• WBC’s also release TF during inflammation

• fast

• factor VII + tissue factor

Blood Vessel Injury

• injured cells expose/releases tissue factor 

  • initiates extrinsic pathway (PT)

• factor XII binds to exposed sub-endothelial collagen

• platelet aggregation (BT) → platelet plug

  • von Willebrand factor

Common Pathway

• factor X converts prothrombin into thrombin 

• thrombin converts fibrinogen into fibrin

Goal of Clotting Cascade

• fibrin mesh stabilizing the platelet plug

  • if there is a problem with any part of the cascade it will take longer for blood to clot

Tissue Factor (TF)

• tissue thromboplastin = factor III

• damaged endothelial cells exposes TF attached to sub-endothelial surface 

• WBC’s release TF during inflammation 

• stimulates platelet aggregation

• initiates the extrinsic pathway (PT)

  • TF binds to factor VIIa to activated factor X (common pathway)

• depleted TF is the initiating factor in Disseminated Intravascular Coagulation

Platelet Type Bleeding

• cause: VWD or thrombocytopenia (low platelets)

• superficial bleeding (petechia) from skin and mucosal surfaces 

  • ex: gingiva, gums, vagina

• epistaxis, purpura (larger than petechia)

• Labs: increase BT (bleeding time)

Factor-Type Bleeding

• ex: hemophilia 

• ecchymosis/hemtoma/burising, hemarthrosis

• Labs: normal BT, platelet plugs are still effective 

  • high PT or aPTT - depending on the condition

Hemophilia

• clotting disorder

• rare x-linked recessive bleeding disorder

  • almost always occurs in males XY, no back up copt to make clotting factor

• certain clotting factors in the blood are either insufficient or missing 

Type A hemophillia

• 80%

• clotting factor VIII

Type B hemophillia

• 15%

• clotting factor IX

• christmas disease

Type C hemophillia

• very rare

• clotting factor XI

• autosomal recessive (m=F)

signs and symptoms of hemophillia

• hematomas, hemarthrosis (severe joint pain due to blood in the joint cavities

Labs for hemophillia

• increased aPTT

• normal PT

• normal BT

• PLT count normal

Treatment for hemophillia

• factor VIII

  • mild - DDAVP, severe - replace factor VIII

• factor IX

  • replace factor IX

Von Willebrand’s Disease

• MC inherited bleeding disorder

  • decreased vWF or abnormal vWF

• autosomal dominant

• decreased platelet aggregation - slow primary hemostasis

• decreased adherence to vascular injury

• incidence 1:100 to 1:1000

Signs and Symptoms of von Willebrand’s Disease

• platelet type bleeding

  • epistaxis, petechia (mucocutaneous bleeding)

  • easy bleeding

• inadequate platelet plug → prolonged bleeding time (increased BT)

Diagnosis of von willebrand disease

• increased BT

• increased aPTT (50% of patients)

• PT normal

• normal platelet count

• vWF level

• Ristocetin cofactor assay - most accurate test

Fibrinolysis

• breaking a clot apart 

• tissue plasminogen activator (TPA)

  • activates plasminogen into plasmin

  • plasmin digests fibrin strands 

  • “clot buster" or “thrombolytic”

    • very useful in treating MI, SVA, PE

D-Dimer Test

• test for fibrin split (degradation) products

• high in DIC, DVT, PE, stroke

Disseminated Intravascular Coagulation (DIC)

• state of hyper coagulation, thrombosis, and hemorrhage occur simultaneously

  • widespread clotting leading to ischemia and multiple end-organ failure in medium/small vessels and microvasculature

  • clotting consumes platelets and clotting factors leading to widespread hemorrhage

Causes of DIC

• sepsis (MCC)

• bacterial fungi, viruses (flu and herpes), cancer

• retained products of conception (RPOC)

• placental abruptions

• anesthesia

• severe bruns

• major trauma 

• transfusion reactions → all cause endothelial damage

Signs and Symptoms of DIC

• factor bleeding and platelet bleeding

• bleeding from IV sites, bruising, petechia 

• shock → hypotension, tachycardia 

Testing of DIC

• increase PT, increase aPTT, increase BT

• decrease platelet count

• increase fibrinogen

• increase d-dimer

• poor prognosis: high mortality rate

Treatment of DIC

• heparin + - cryprecipitate + try to keep them alive

• no heparin in sepsis

DIC initiating mechansim

• release of TF (tissue factor or tissue thromboplastin) into circulation

• TF not normally in contact with blood

Bleeding Time (BT)

measures the response of platelets to a vascular injury (has nothing to do with the coagulation cascade)

Prothrombin Time (PT)

extrinsic pathway (tissue factor and factor VII)

• important in monitoring warafin (Coumdin) therapy

Activated Partial Thromboplastin Time (aPTT)

intrinsic pathway (factor VIII and factor IX)

• important in monitoring therapy