Clin Med: Heme/Onc

What is hematopoiesis?

blood cell formation

What is the average RBC lifespan?

120 days

What is the average platelet lifespan?

8-9 days

What is the average neutrophil lifespan?

5-90 hours

What is the cell of origin for all blood cells?

Pluripotent stem cell

- it can differentiate into all of the distinct cell lines

- only cell that can self-renew

What is a normal hemoglobin in males?

14-16 gms/dL

What is a normal hemoglobin in females?

13-15 gms/dL

What is the normal MCV of a RBC?

80-95 fl

What is normo-normo anemia? What are some diseases?

RBCs that are normal in size and Hgb content but insufficient in number

Diseases:

-Aplastic anemia

-Post-hemorrhagic anemia

-Hemolytic anemia

-Anemias of chronic dz

-Myelophthisic anemia

What is anemia of chronic disease?

- "anemia of inflammation"

- associated with chronic disease states like infections, malignancy, diabetes, or autoimmune disorders

- impairment in the transfer of storage iron (you have iron but cannot use it, therefore, not a true iron def.)

S/S of anemia of chronic disease

- mild sx like fatigue, pallor, SOB, poor concentration, exercise intolerance

Dx of anemia of chronic disease

-↑ ferritin

-↓ TIBC (transferrin: iron stores)

-↓ serum iron

-↓ reticulocyte

- ↓ serum erythropoietin

Tx of anemia of chronic disease

- tx underlying dz

- if severe, RBC transfusion or EPO injection

What is folic acid deficiency?

- blood lacks vit B9(folate) for RNA and DNA synthesis

- macrocytic normochromic anemia

S/S of folic acid deficiency?

- NO neurological sx

- common alcoholics & chronically malnourished

- risk of neural tube birth defects

- cheilosis/glossitis (sore tongue & scales/fissures on corners of lips)

- stomatitis

- buccal mucosa & tongue ulcers

Dx of folic acid deficiency?

-↓ Serum B12

-↓ Serum Folate (short-term, based on what you recently ate)

-↓ RBC Folate (more accurate bc measures long-term)

- increased homocysteine and normal methylmalonic acid (diff than vit b12)

- CBC and peripheral smear shows increased MCV, macroovalocytes

TX of folic acid deficiency?

- oral folate 1mg daily

- women of childbearing age = 4mg daily

What is vit B12 deficiency?

- Autoantibodies → ↓ IF function and ↓ gastric parietal cell HCl production

- "pernicious anemia"

- macrocytic anemia

S/S of vitamin B12 deficiency?

- neurological sx due to nerve demyelination like paresthesias and numbness

- beefy red tongue

DX of vit B12 deficiency?

- ↑ MCV

- ↑ MMA

TX of vit B12 deficiency?

- B12 replacement

What are intrinsic hemolytic anemias?

RBC destoryed bc:

- RBC membrane defects like hereditary spherocytosis

- enzyme deficiencies like G6PD and pyruvate kinase

- hemoglobin abnormalities like sick cell

What are extrinsic hemolytic anemias?

RBCs are normal but destroyed by autoantibodies

What is hereditary spherocytosis?

- defect in spectrin and ankyrin RBC membrane proteins

- abnormal shape gets trapped and destroyed in spleen = extravascular hemolysis

Dx & Tx of hereditary spherocytosis?

- ↑ reticulocute count

- blood smear: spherocytes

- tx: splenectomy

What is G6PD deficiency?

- MC human enzyme defect (black US males)

- triggered by infxn, oxidative stress, fava beans, antimalarials

- blood smear: bite cells & Heinz bodies

What is pyruvate kinase deficiency?

- autosomal recessive disorder causing dehydrated RBCs > Burr cells

- lack of ATP production > abnormal shape > gets trapped and destroyed in spleen = extravascular hemolysis

What is thalassemia?

-Decreased production of alpha or beta globin chains > decreased quantity of normal hemoglobin

What populations are most often affected by thalassemia?

α-thalassemia: Southeast Asian or Chinese

β-thalassemia: Mediterranean

What is alpha thalassemia?

-If <3 genes deleted → mild anemia

-If all 4 genes → incompatible with life (hydrops fetalis)

Tx of alpha thalassemia?

- do NOT give iron

What beta thalassemia?

-Beta minor (most common) - asx or mild anemia

-Beta major (both genes deleted) - severe anemia

Dx of beta thalassemia?

- Minor: ↑ HbA2 levels

- Major: ↑ HgF and HgbA2

-Radiograph: skull bossing with "hair on end appearance"

Tx of beta thalassemia?

- major: frequent transfusion, vit C, folate supplementation

What is iron deficiency anemia?

- MCC of anemia world wide

- ↓ absorption (diet)

- Chronic blood loss (menstruation #1, GI bleed #2)

- ↑ metabolic requirement (children, pregnancy)

S/S of iron deficiency anemia?

- pica, pagophagia

- koilonychia

- glossitis

Dx of iron deficiency anemia?

- microcytic hypochromic

- ↓ serum iron

-↓ ferritin

-↑ TIBC > 400 (transferrin)

-↓ transferrin saturation

Tx of iron deficiency anemia?

- ferrous sulfate w/ vit C (AE: constipation, GI upset, dark stool)

What is aplastic anemia?

- autoimmune disorder

- injury to hematopoietic stem cells > bone marrow aplasia > pancytopenia

- normocytic-normochromic

S/S of aplastic anemia?

- bleeding

- hypoxia

- frequent infxns

- easy bruising

Dx of aplastic anemia?

- ↓ WBCs, ↓ RBCs

- BM biopsy: hypocellularity, fatty bone marrow

Tx of aplastic anemia?

- BM transplant

- immunosuppressants

What is post-hemorrhagic anemia?

- acute blood loss

- normocytic-normochromic

- tx: IV fresh whole blood or plasma

What is myelophthisic anemia?

- widespread destruction of bone marrow (metastasic cancer)

What is hemochromatosis?

autosomal recessive disease causing excess deposition of iron

-liver is primary target organ

S/S of Hemochromatosis

- cirrhosis

- "bronze diabetes" (skin pigmentation)

Dx Hemochromatosis

↑ serum iron

↑ ferritin

Tx Hemochromatosis

- phlebotomy

- deferoxamine (iron-chelating agents

What is sickle cell anemia?

- autosomal recessive disorder causing abnormal hemoglobin (HbS; a2S2)

S/s of sickle cell anemia

- pain and anemia is HALLMARK

-vaso-occlusive pain crisis (long bones), priapism

- spenic sequestration crisis: acute splenomegaly, rapid ↓ Hgb

Young children with sickle cell anemia are asplenic due to infarcts (spleen removed), what typically puts them in aplastic anemia crisis due to high susceptibility to infection?

parvovirus B19 (causes 5th's disease/slapped cheek disease)

What infections are the MCC of acute chest syndrome in sickle cell patients?

chlamydia and mycoplasma pneumoniae and

Dx sickle cell anemia

- hemolytic anemia: ↓Hbg

- howell jolly bodies-basophilic nuclear remnant in the RBC

- Hgb electrophoresis: HbSS, no HbA

Tx for sickle cell anemia

- opiods (drug of choice)

- hydroxyurea for prevention

What is von willebrand disease?

- Deficient or defective vWF → ineffective platelet adhesion

- Most common hereditary bleeding disorder

S/s of von willebrand disease

- Mucocutaneous bleeding

- Prolonged bleeding

Dx von willebrand disease

- ristocentin cofactor tests

- prolonged or normal bleeding time, low VFW

- no change in PT,PTT, INR (btwn 2.5-3.5)

Tx for von willebrand disease

Desmopressin

What is hemophilia A (Factor VIII) deficiency and hemophilia B (Christmas disease, Factor IX)?

- X-lined recessive, primarily in males

- Hemophilia A: Lack of Factor VIII (8) → failure to clot

- Hemophilia B: Lack of Factor IX (9) → failure to clot

S/s for hemophilia A (Factor VIII) and hemophilia B (Christmas disease, Factor IX)

- Hemarthrosis (delayed bleeding after trauma)

- Excessive hemorrhage due to trauma

Dx hemo A and hemo B

↑ PTT

tx for hemo A and B

factor replacement

What is hemo C and who does you see it in?

8% Ashkenazi jews

Factor XI deficiency

presentation for hemo C

- bleeding after surgery

- no spontaneous hemarthroses

Etiology for vitamin K def

- Dietary deficiency (dark leafy vegetables, fat malabsorption)

- chronic abx use: minocycline

dx vitamin k def.

PT prolonged > PTT

tx for vitamin k def.

- Vit K PO or IV

What is coagulopathy of liver disease?

- Liver is site of synthesis of most coag factors, so liver disease compromises the factor synthesis

dx coagulopathy of liver disease

- PT prolonged > PTT

tx for coagulopathy of liver disease

no response to Vit K

Who would you see DIC in?

very ill patients - sepsis, massive trauma, neoplasm, complications of birth

What is the most common aquired hypercoagulable state in hospitalized pts?

DIC

s/s of DIC

- excessive bleeding

- excessive thrombosis

dx DIC

DIC panel!!!

↓ Platelets

↓ fibrinogen

↑ PTT/PT and D-Dimers

- Schistocytes on smear

- microangipathic hemolytic anemia

tx for DIC

treat underlying cause

what is thrombocytopenia?

-Low platelet count

-Platelets 20-50K → minimal bleeding risk unless

-Platelets <10,000 → risk of spontaneous bleeding

s/s for thrombocytopenia

- petechiae

- ecchymoses

- nose bleed

- mucosal bleeding

causes for thrombocytopenia

↓ platelet production

↑ platelet destruction

↑ sequestration (platelets pool somewhere)

tx for thrombocytopenia

- transfusions

- treat underlying cause

what is idopathic thrombocytopenia purpura?

- Acquired, immune-mediated isolated thrombocytopenia

- Antiplatelet antibodies → splenic destruction of platelets

s/s of idopathic thrombocytopenia purpua

- Mucocutaneous bleeding (bleeding gums, epistaxis)

- NO splenomegaly

dx idiopathic thrombocytopenia purpura

- Isolated thrombocytopenia (no schistocytes)

- Normal coag studies (aPTT, PT, INR btwn 2.5-3.5)

- Bone marrow biopsy: megakaryocytes (immature platelets

tx idiopathic thrombocytopenia purpura

- Glucocorticoids

- IVIG (IV immunoglobulin)

What is thrombotic thrombocytopenia purpura?

- deficiency in von willebrand factor cleaving protease (VWFCP or ADAMTS-13) > platelets aggregate (made up of hylain/vWF protein and platelets, no fibrinogen

- MC due to auto-antibodies

s/s for TTP

FAT RN

-Fever (rare)

-Anemia (microangiopathic hemolytic anemia)

-Thrombocytopenia (mucocutaneous bleeding)

-Renal failure

-Neuro sx

dx TTP

- low platelets

-Normal coag studies (aPTT, PT, INR between 2.5-3.5)

- schistocytes

- microangipathic hemolytic anemia

tx for TTP

- plasma exchange ASAP (first line)

- no platelets

what is hemolytic uremic syndrome?

- MC in children with recent hx of gastroenteritis

- microemboli in vessels throught the body

- MC kidneys > kidney failure

s/s of hemolytic uremic syndrome

- prodromal diarrhea

- renal manifestations

dx of hemolytic uremic syndrome

- Labs: thrombocytopenia w/ normal coag studies (PT, PTT, fibrinogen)

- ↑ BUN and creatinine (kidney function)

tx for hemolytic uremic syndrome

- Supportive therapy mainstay of tx

- Abx usually avoided bc may worsen

What is heparin induced thrombocytopenia?

- immune mediated reaction to heparin which crossreacts and destroys platelets

- hypercoagulability

s/s of HIT

1. Timing (thrombocytopenia 7-10 days post-initiation of heparin)

2. Thrombus: new thrombus formation despite heparin tx

3. Thrombocytopenia degree (>50% drop from baseline)

dx HIT

- heparin platelet factor 4 antibody

- usually cant wait for results; need to tx for high sus.

tx for HIT

d/c heparin, begin IV argatroban

what is antithrombin III def.?

↓ levels of antithrombin III (AT III) → hypercoagulability

s/s of antithrombin III def.

↑ incidence of venous thromboembolism - DVT & PE

tx for antithrombin III def.

Anticoagulants only before surgical procedures

what is factor V leiden?

- Most common inherited thrombophilia/hypercoagulability in Caucasians

- mutated factor V is resistant to breakdown by activated protein C

s/s of factor V leiden?

↑ incidence of DVT, PE, hepatic vein or cerebral vein thrombosis