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Hematology Flashcards

1
Q

RBC

A

heme: iron is part of heme, binds/releases O2
globin: made of 4 subunits; in adult hgb (HgbA) there are 2 alpha chains and 2 beta chains

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2
Q

Iron*

A

TRANSFERRIN: binds to free Fe to reduce oxidative damage assoc w/ free Fe - TRANSPORTS Fe throughout body

TIBC: indirect way to measure transferrin levels (total iron-binding capacity)

FERRITIN: most Fe not used for hgb synthesis is stored in ferritin protein molucule
-FERRITIN = FE STORES

SERUM FE: measures amount of Fe bound to transferrin

Labs Interpretation:

  • INC TRANSFERRIN + INC TIBC –> Iron Deficiency (more transferrin leads to dec transferrin saturation)
  • DEC TRANSFERRIN + DEC TIBC –> anemia of chronic disease; transferrin an acute phase reactant aimed at decreasing Fe available for microbes, may also be decreased in iron-overload states
  • DEC FERRITIN: Iron-deficiency anemia (pt w/ reduced Fe use up their stores first, decreased stored Fe)
  • INC FERRITIN: anemia of chronic disease (inc ferritin sequesters iron, reduce serum Fe levels available to bacteria)
  • DEC SERUM FE: seen w/ both Iron Deficiency anemia (dec total body Fe) and Anemia of Chronic Dz (lowering of serum Fe)
  • best way to distinguish btw Fe deficiency and anemia of chronic disease is by TIBC + Ferritin:
  • FE DEFICIENT ANEMIA: DEC SERUM FE, DEC FERRITIN, INC TIBC (use up stores –> dec ferritin, and inc bind capacity)

-ANEMIA OF CD: DEC SERUM FE, INC FERRITIN, DEC TIBC
(body makes more ferritin to pick up Fe from serum so not available for mo, binding capacity low bc most ferritins are occupied)

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3
Q

Fe-related Acute Phase Reactants / labs*

A

Responses meant as acute response but in chronic diseases, persist, and lead to anemia due to reduced serum Fe and decreased Fe availability for hgb production

  • DEC TRANSFERRIN + DEC TIBC –> anemia of chronic disease; transferrin an acute phase reactant aimed at decreasing Fe available for microbes, may also be decreased in iron-overload states
  • INC FERRITIN: anemia of chronic disease (inc ferritin sequesters iron, reduce serum Fe levels available to bacteria)
  • INC HAPTOGLOBIN: binds free hgb, reducing Fe available for mo
  • INC CRP: marker inflam/infx –> causes mo destruction by inc opsonization (marking cell for destruction by macros)
  • INC HEPCIDIN: prevents Fe release from macrophages, reducing Fe available for mo
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4
Q

hemolytic anemias - types

A

anemia caused by inc RBC destruction when rate of destruction exceeds BM ability to replace cells

Intrinsic (Inherited Disorders):

  • Sickle Cell
  • Thalassemia
  • G6PD deficiency
  • Hereditary spherocytosis

Extrinsic (Acquired Disorders):

  • Autoimm Hemolytic Anemia
  • DIC
  • TTP
  • HUS
  • Paroxysmal nocturnal hemoglobinuria
  • Hypersplenism
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5
Q

hemolytic anemias - general findings

A

RETICULOCYTOSIS: BM release immature RBC

INC LDH: enzyme found in abundance in RBCs, inc RBC destruction leads to inc serum LDH

INC INDIRECT BILIRUBIN: inc RBC destruction overwhelms liver’s UGT enzyme conjugating ability, there will be inc indirect bili –> +/-JAUNDICE
-sometimes inc direct bilirubin –> dark urine

DEC HAPTOGLOBIN: inc RBC destruction leads to INC FREE HGB –> HAPTOGLOBIN BINDS to reduce oxidative toxicity; when haptoglobin used up, levels are low

+SHISTOCYTES ON PERIPHERAL SMEAR: fragmented RBC from destruction in spleen, liver or small BV (ex small BV thrombosis –> DIC, TTP, HUS)

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6
Q

Anemia Basics

A

3 causes of anemia: increased blood loss, increased RBC destruction, decreased RBC production

  • sx-
  • CARDIO: palp, tachy, ortho/hypo, high output HF, syncope
  • PULM: SOB, tachy, chest pain
  • SKIN: pallor, pale conjunctiva, purpura, petechiae
  • NEURO: HA, neuropathies, AMS, vertigo
  • ABDOMEN: hepatosplenomegaly, ascites, +hemoccult bld
  • dx-
  • CBC w/ RBC indices: hgb, hct, MCV, MCH, RDW, RBC
  • peripheral blood smear; BM BX GOLD STANDARD
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7
Q

Anemia: Lab –> Morphologic Approach**

A
  1. RETIC COUNT
  • INC: brisk BM response to HEMOLYSIS OR BLOOD LOSS
  • -> BLOOD LOSS: tissue or occult loss
  • -> HEMOLYSIS: intrinsic/hereditary or extrinsic/acquired

-DEC: DEFICIENT RBC PRODUCTION (reduced BM response) –> LOOK AT MCV

–> MICROCYTIC (<80): IRON DEFICIENT, LEAD, THALASSEMIA, EARLY Anemia Chronic Dz

–> NORMOCYTIC (80-100): ANEMIA CHRONIC DZ, renal, mixed, endocrine, dilutional, early Fe deficiency

–>MACROCYTIC (>100): B12, FOLATE, liver dz, etoh, hypothyroidism; myelodysplastic syndrome, acute leukemia

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8
Q

B12 (cobalamin) Deficiency**

A
  • stomach acids release B12 from food + binds to IF for absorption in TERMINAL ILEUM
  • B12 deficiency causes ABNORMAL SYNTHESIS OF DNA, nucleic acid and abnormal metabolism of erythroid precursors
  • etiologies:
  • PERNICIOUS ANEMIA: AUTOIMM DESTRUCTION/LOSS OF GASTRIC PARIETAL CELLS that secrete IF
  • Vegans
  • MALABSORPTION: ETOHism, diseases affecting ileum
  • Dec IF production: acid-reducing drugs, gastric sx, atrophic gastritis
  • sx- NEURO SX: PARESTHESIAS, GAIT ABNORMAL, MEMORY LOSS, DEMENTIA
  • GI: anorexia, D, glossitis, anemia
  • dx-
  • labs: INC MCV (>115), HYPERSEGMENTED NEUTROPHILS, inc homocysteine, inc methylmalonic acid, dec B12 levels
  • PERNICIOUS ANEMIA: +IF antibodies, parietal cell Ab, inc gastrin level, +SHILLING TEST

-tx- IM or subQ B12 to start –> WATCH FOR SIGNS OF HYPO-K (replacement leads to retics w/ new cells taking up lots of potassium)

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9
Q

Folate (Vitamin B9) Deficiency*

A
  • folate absorption occurs in jejunum; stores last ~4 mo
  • folate required for DNA synthesis
  • etiologies: malabsorption, pregnancy, hemolysis (inc cell turnover), meds (methotrexate, bactrim, phenytoin)
  • sx- similar to B12 but no neurological abnormalities, GLOSSITIS
  • dx- INC MCV (>115), HYPERSEGMENTED NEUTROPHILS
  • dec folate, normal B12, inc serum homocysteine only
  • tx- FOLIC ACID 1 MG PO DAILY
  • replacing folate if it is B12 deficiency will correct anemia but neuro sx will worsen*
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10
Q

general causes for microcytic anemia

A
  • dec iron availability (Fe deficiency, anemia CD, copper dz)
  • dec heme production (lead poison, sideroblastic anemia)
  • dec globin production (thalassemia, hgb-opathies)
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11
Q

Iron Deficiency Anemia**

A

Etiologies:

  • CHRONIC BLOOD LOSS: excessive periods, occult (colon ca, parasitic hookworms)
  • dietary deficiency/inc requirements: pregnancy, rapid growth, infants breastfed

-sx- PAGOPHAGIA (ICE CRAVE), PICA, ANGULAR CHEILITIS, KOILONYCHIA (nail spooning)

  • dx- DEC FERRITIN, INC TIBC, DEC SERUM FE
  • INC RDW (dec RBC count/hgb/hct +/- dec MCV)
  • DEC TRANSFERRIN SATURATION, dec reticulocytes
  • tx- IRON REPLACE
  • Ferrous sulfate 325 mg PO daily, best on empty stomach; Vit C increases absorption
  • replace assoc w/ SE: N/V/C, cramps - start low and inc
  • SUPPLEMENT –> INC RETIC COUNT WITHIN 7 DAYS
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12
Q

Lead Poisoning Anemia*

A
  • lead poisoning causes cell death, shortens lifespan of RBCs and inhibits multiple enzymes needed for heme synthesis –> ACQUIRED SIDEROBLASTIC ANEMIA
  • sx- ABD PAIN W/ CONSTIPATION, NEUROLOGIC SX (ataxia, fatigue, learning disabilities, coma, shock), anemia sx, metabolic acidosis +/- asymptomatic
  • dx-
  • INC SERUM LEAD + INC SERUM FE; dec TIBC, inc ferritin (looks like anemia cd but serum fe increased)
  • Peripheral Smear: MICROCYTIC, HYPOCHROMIC ANEMIA W/ BASOPHILIC STIPPLING (dots of denatured RNA)
  • RINGED SIDEROBLASTS in BM (iron accum in mitoch)
  • xray: LEAD LINES (linear hyperdensities at metaphyseal plates, LEAD LINES IN GUMS OF ADULTS
  • tx- remove source of lead; CHELATION TX IF SEVERE
  • Treatment is oral succimer or IV EDTA (calcium disodium edetate, given after dimercaprol)
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13
Q

thalassemia overview*

A
  • decreased production of globin chains
  • GENETIC BENEFIT AGAINST MALARIA

Normal: after 6 mo old, adult Hgb is predominant

  • HgbA (adult): 2 alphas, 2 betas - 95%
  • HgbA2: 2 alphas, 2 deltas - 1.5-3%
  • HgbF (fetal): 2 alphas, 2 gammas - trace

-THINK THALASSEMIA IF MICROCYTIC ANEMIA W/ NORMAL OR INC SERUM FE OR NO RESPONSE TO INC IRON

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14
Q

alpha thalassemia*

A

Decreased alpha-globin chain production; 4 genes determine it
-mc SE asians

  • Silent Carrier: 1/4 genes - clinically normal
  • Alpha Thal Minor/Trait: 2/4 - mild microcytic anemia
  • Alpha Thal Intermediate (Hgb H Dz): 3/4 - chronic anemia, pallow, hepatosplenomegaly, frontal maxilla bony overgrowth, frx, pigmented gallstones, iron overload
  • Hydrops Fetalis: 4/4 - stillbirth or death shortly after –> Barts Hgb (4 gamma-globins)
  • dx-
  • CBC: hypochrom, microcytic (60-75 - smaller than Fe def)
  • normal or inc RBC count, normal or inc serum Fe/stores
  • Hgb may be as low as 3-6
  • Periph Smear: TARGET CELLS, teardrop cells, basophilic stippling
  • HEINZ BODIES IN HGB H DISEASE (insoluble B-chain x4)
  • HgB Electrophoresis

-tx-
-mild (a-trait) - no tx needed
-moderate: folate (if retic count high), avoid Fe supplement
-severe: blood transfusions weekly, vit c, folate supplement
Iron-chelating agents (prevents Fe overload), +/-splenectomy
-allogeneic BM transplant is the definitive tx of major

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15
Q

beta thalassemia*

A

Decreased production of beta-globulin chains –> excess a-chains
-MC IN MEDITERRANEAN, AFRICANS

-Trait (minor): 1/2 abn alleles - usually asymptomatic, +/- mild to mod anemia (50% decrease in B synthesis)

  • Intermedia: mild homozygous form - milder sx than major
  • -> hepatosplenomegaly, anemia, bony disease

-Major (Cooley’s anemia): 2/2 abn alleles - usually asymptomatic at birth (bc of hgbF) but BECOME SYMPTOMATIC AT 6 MONTHS –> ineffective erythropoiesis, erythroid hyperplasia, FRONTAL BOSSING + MAXILLARY OVERGROWTH, HEPATOSPLENOMEGALY, SEVERE HEMOLYTIC ANEMIA, osteopenia, Fe overload, pigmented gallstones

  • dx-
  • Electrophoresis:
  • Trait/Minor: Inc HgbF, Inc HgbA2, Dec HgbA (dec B chain)
  • Cooleys/Major: Inc HgbF (up to 90%), inc HgbA2, little to no HgbA

Skull X-rays: bossing w/ “hair on end appearance” due to extramedullary hematopoiesis

  • tx- MAJOR
  • periodic blood transfusions, Vit C, folate supplementation, avoid excess Fe intake
  • Iron-chelating agents: IV Deferoxamine, PO Deferasirox
  • Splenectomy if refractory
  • Allogenic BM transplant definitive
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16
Q

anemia of chronic disease

A

Normocytic
Infx, inflammation, auto immune, malignancy → decreased RBC production vs. increased loss

  • Primary mechanism is decreased RBC production
  • Decreased serum Fe to prevent availability to pathogens
  • Lactoferrin from macrophages binds Fe better than transferrin and may shunt iron away from RBCs
  • Hepcidin: produced by liver; inhibits macrophage Fe release
  • Increased ferritin –> sequesters iron in storage

-dx-
↓ serum iron, TIBC, ↑ (or normal) ferritin
-GOLD STD: BM Fe STORE STUDY

-tx-
Tx underlying disease, supportive care
Erythropoietin-A if renal disease

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17
Q

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency*

A

G6PD is protective enzyme to RBC against oxidative stress –> w/out it, oxidative stress oxidizes Hgb into methemoglobin (doesn’t carry O2 well) –> inc RBC membrane damage/fragility and denatured Hgb –> DENATURED HGB PRECIPITATES AS HEINZ BODIES which target them for destruction by spleen –> EPISODIC HEMOLYTIC ANEMIA
-Sex-linked; MC males and AA

-Stressors: INFX MC, FAVA BEANS, SULFA DRUGS, ANTIMALARIALS, fluoroquinolones, nitrofurantoin, asa, mothballs

  • sx- EPISODIC ACUTE HEMOLYTIC ANEMIA
  • back or abd pain, jaundice, SPLENOMEGALY
  • splenic RBC sequestration –> HEMOLYTIC CRISIS
  • dx-
  • peripheral smear: in crisis, NORMOCYTIC HEMOLYTIC ANEMIA: SCHISTOCYTES, +- HEINZ BODIES
  • labs: inc retic, inc indirect bili, dec haptoglobin, G6PD ENZYME ASSAY

Tx: stop offending agents, hydrate, no more drug
-severe anemia: Iron/Folic acid supplement +/- blood trans

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18
Q

sickle cell disease**

A
  • Sickle Cell Disease: auto-recessive disorder of HgbSS –> valine subs for glutamic acid on the beta chain (point mutation), 0.15% of AA
  • Sickle Cell Trait: HETEROZYGOUS HgbS (AS) –> 8% of AA, confers some resistance to malaria (plasmodium falciparum); usually asymptomatic unless exposed to severe hypoxia/dehydration, MAY HAVE EPISODIC HEMATURIA AND INABILITY TO CONCENTRATE URINE
  • patho- dec solubility of Hgb S under hypoxic conditions –> RBC sickling causes micro thrombosis and hemolytic anemia (sickled cells destroyed by spleen)
  • sx-
  • BEGIN @ 6 MO; DACTYLITIS MC 1ST SX (swelling of digits)
  • INF: OSTEOMYELITIS (ESP SALMONELLA), FUNCTIONAL ASPLENIA, APLASTIC CRISIS ASSOC W/ PARVO B19, folate deficiency
  • Hemolytic anemia: gallstones, jaundice
  • MICROTHROMBOSIS (INFARCTS):
  • Skeletal: H-SHAPED VERTEBRAE, ischemic necros of bones (like femoral and humeral head)
  • SPLENIC SEQUESTRATION CRISIS –> acute splenomegaly and rapidly dec Hgb –> SPLENIC INFACT (FX ASPLENIA)
  • SKIN ULCERS esp on tibia
  • PAINFUL OCCLUSIVE CRISES: triggered by cold, hypoxia, infx, dehydration, ETOH, pregnancy, ABRUPT PAIN, renal or hepatic dysfx, PRIAPISM
  • dx-
  • CBC: dec Hgb, dec Hct, inc retic
  • Smear: target cells, sickled cells, +HOWELL-JOLLY BODIES (indicates fx asplenia)
  • ELECTROPHORESIS: GOLD STANDARD
    • Disease: HgbS, no HgbA, inc HgbF
    • Trait: HgbS, dec HgbA

-tx-
-IV HYDRATION AND O2 FIRST STEP IN PAIN CRISIS (reverses/prevents sickling)
-NARCOTICS for pain, avoid meperidine
+/-RBC TRANSFUSION IN SEVERE

  • HYDROXYUREA - reduces freq of pain crisis (inc RBC water, dec RBC sickling, inc HgbF - resistant to sickling)
  • FOLIC ACID - needed for RBC production and DNA synth
  • CHILDREN IMMUNIZE FOR S.PNEUMOCOCCUS, Hib, N.MENINGOCOCCUS
  • CHILDREN: PROPHYLACTIC PCN UNTIL 6 YO
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19
Q

hereditary spherocytosis (HS)*

A

Autosomal dominant - intrinsic hemolytic anemia

  • RBC MEMBRANE/CYTOSKELETON DEFECT –> INC CELL FRAGILITY AND SPHERE-SHAPED RBCs –> INC RBC HEMOLYSIS BY SPLEEN
  • aplastic crisis if infected w/ ParvoB19
  • sx-
  • hemolysis: anemia, jaundice, SPLENOMEGALY, pigmented black gallastones

-dx-
-Smear: HYPERCHROMIC MICROCYTOSIS (80% SPHEROCYTES)
+OSMOTIC FRAGILITY TEST, COOMBS NEGATIVE

  • tx-
  • FOLIC ACID (not curative but helpful - maintains RBC production and DNA synthesis)
  • SPLENECTOMY TX OF CHOICE IN SEV DISEASE
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20
Q

autoimmune hemolytic anemia (AIHA)*

A

AB ON RBC’s OWN SURFACE –> inc destruction by macrophages and spleen
-IDIOPATHIC MC, meds +/- warm or cold

-Warm Agglutinins: IgG Ab causes splenic macrophage RBC destruction via phagocytosis @ core body temp –> autoimmune (SLE, RA), malignancy (CLL)

  • Cold Agglutinins: IgM Ab vs. RBC induces intravascular complement-mediated RBC lysis, esp at cold temps - may follow infx (MYCOPLASMA, EBV, HIV), malignancy
  • anemia, ACROCYANOSIS, fatigue, dyspnea, +/-Raynauds

-dx-
+DIRECT COOMBS TEST (separates from hereditary type)
-Smear: MICROSPHEROCYTES, polychromasia, RBC agglutination

  • tx-
  • WARM: CORTICO 1ST LINE –> splenectomy or Rituximab
  • COLD: AVOID COLD EXPOSURE –> +/- Rituximab
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21
Q

paroxysmal nocturnal hemoglobinuria*

A

RARE, ACQUIRED STEM CELL MUTATION –> RBCs deficient in GPI anchor surface protein that protects RBC from complement –> INC COMPLEMENT-MEDIATED RBC DESTRUCTION AND THROMBOSIS

  • sx-
  • HEMOLYTIC ANEMIA - DARK COLA URINE during night or early am w/ clearing during the day
  • VENOUS THROMBOSIS OF LARGE VESSELS - free Hgb binds w/ nitric oxide, decreased NO levels lead to hypercoag state –> thrombosis in uncommon veins
  • PANCYTOPENIA - protein deficiency in RBC, WBC, platelets –> bone marrow failure
  • dx-
  • FLOW CYTOMETRY BEST SCREEN
  • osmotic fragility test, Coombs Neg
  • may progress into myelodysplasia and AML
  • tx-
  • ECULIZUMAB (anti-complement C5 ab)
  • Prednisone dec hemolysis; BM transplant
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22
Q

primary hemostasis

A

PLATELETS form plug at site of vascular injury –> PLATELET ADHESION, ACTIVATION (send out ADP + thromboxane A2 which attracts other platelets) AND AGGREGATION (forming a plug)

  • dz examples: thrombocytopenia (ITP, TTP, HUS, DIC, vWD)
  • DISORDERS THAT AFFECT PLATELETS WILL AFFECT PRIMARY HEMOSTASIS, bleeding time;
  • PT + PTT USUALLY UNAFFECTED

-sx- PETECHIAE + MUCOCUTANEOUS BLEEDING

23
Q

secondary hemostasis

A

CLOTTING FACTORS respond in cascade to form FIBRIN STRANDS THAT STRENGTHEN THE PLATELET PLUG (from primary hemostasis)

  • dz examples: hemophilia, DIC, vWD
  • disorders affecting the EXTRINSIC PATHWAY –> PROLONGS PT and affecting the INTRINSIC PATHWAY –> PROLONGS PTT

-sx- DEEP DELAYED BLEEDING (HEMARTHROSIS) + DELAYED BLEEDING AFTER SURGERY

24
Q

extrinsic vs intrinsic pathway

A

Extrinsic: activated OUTSIDE the BV; Factor 7 leaves open BV and comes in contact w/ tissue factor (TF)
-prolonged PT

Intrinsic : damage to surface “within” BV activates intrinsic
-prolonged PTT

25
Q

PTT (partial thromboplastin time)*

A

measures efficacy of INTRINSIC and common coag pathway

  • normal PTT time requires Factors 1, 2, 5, –> 8, 9, 11, 12!
  • PROLONGED: HEPARIN, DIC, vWD, HEMOPHILIA A/B
26
Q

PT (prothrombin time)*

A

measures EXTRINSIC (tissue factor) pathway and common pathway

  • normal PT times require Factors 1, 2, 5 –> 7 + 10!
  • PROLONGED: WARFARIN TX, VITAMIN K DEFICIENCY, DIC
27
Q

thrombotic thrombocytopenic purpura (TTP)*

A 
Dec ADAMTS13 (a vWF cleaving protease) --> large vWF adhere to platelets and causes endothelial platelet adhesion --> SMALL VESSEL THROBOSIS --> damage/shear the RBC (HEMOLYTIC ANEMIA)
-MC FEMALE
  • Primary TTP: IDIOPATHIC –> Ab vs. ADAMTS13
  • Secondary TTP: malignancy, BM transplant, SLE, estrogen, pregnancy, HIV
  • sx- Pentad:
  • THROMBOCYTOPENIA (petechiae, bruising, mucocutaneous bleeding - skin, oral, epistaxis, GI/GU)
  • MICROANGIOPATHIC HEMOLYTIC ANEMIA (anemia, jaundice, fragmented rbc/schistocytes on smear)
  • KIDNEY FAILURE/UREMIA (not as common)
  • NEURO SX (HA, CVA, AMS)
  • FEVER (rare)
  • dx-
  • labs: THROMBOCYTOPENIA, NORMAL PT/PTT
  • hemolytic anemia –> Smear: inc retics, schistocytes
  • SPLENOMEGALY

-tx-
-PLASMAPHERESIS TX OF CHOICE
-IMMUNOSUPPRESION - CORTICOSTEROIDS
-no platelet transfusions (may cause thrombi formation)
+/- splenectomy if refractory

28
Q

hemolytic uremic syndrome*

A

PLATELET ACTIVATION BY EXOTOXINS
-toxins from infx –> damage vascular endothelium & activates platelets (microthrombi) –> platelets get depleted –> thrombocytopenia
(toxins preferentially damage kidney, small vessel thrombosis cause RBC damage as they circulate/shear = hemolytic anemia)

  • MC W/ CHILDREN; usually preceded by ENTEROHEMORRHAGIC E.COLI 0157, SHIGELLA OR SALMONELLA *suspect in children w/ renal failure w/ diarrhea prodrome
  • adults: seen w/ HIV, SLE, antiphospholipid synd
  • sx- Triad:
  • THROMBOCYTOPENIA (petechiae, bruising, purpura)
  • MICROANGIOPATHIC HEMOLYTIC ANEMIA (anemia, jaundice, fragmented rbc/schistocytes on smear)
  • KIDNEY FAILURE/UREMIA (MORE COMMON THAN TTP)
  • lacks fever and neuro sx seen in TTP but labs similar
  • dx- INC BUN/CREATININE and…same as TTP
  • labs: THROMBOCYTOPENIA, NORMAL PT/PTT
  • hemolytic anemia –> Smear: inc retics, schistocytes
  • SPLENOMEGALY
  • tx-
  • OBSERVATION IN MOST (IV fluids for renal perfusion)
  • PLASMAPHERESIS +FFP if severe, or complications
  • ABX MAY WORSEN CONDITION (INC VEROTOXIN RELEASE BC OF CELL LYSIS)
29
Q

disseminated intravascular coagulation (DIC)*

A

PATHOLOGICAL ACTIVATION OF COAGULATION SYSTEM –> WIDESPREAD MICROTHROMBI (consumes coag proteins) + platelets –> SEVERE THROMBOCYTOPENIA: DIFFUSE BLEEDING from skin, resp tract, GI tract

  • INFX: GRAM NEG SEPSIS MC
  • MALIGNANCIES - AML, lung or GI cancer, prostate ca
  • OBSTETRIC - preeclampsia, abruption, septic abortion
  • massive tissue injury (burns), liver dz, viral, aortic aneurysm
  • sx-
  • WIDESPREAD HEMORRHAGE –> VENIPUNCTURE SITES
  • THROMBOSIS - renal, hepatic, resp dysfx, GANGRENE
  • dx-
  • INC THROMBIN FORMATION: DEC FIBRINOGEN, INC PTT/PT/INR, SEV THROMBOCYTOPENIA
  • Smear: fragmented RBC/schistocytes
  • INC FIBRINOLYSIS = INC D-DIMER
  • tx-
  • treat underlying cause!
  • FFP IF SEVERE BLEEDING +/- platelet transfusion
  • thrombosis: +/- heparin in severe cases
30
Q

idiopathic (autoimmune) thrombocytopenic purpura (ITP)*

A

Acquired, abnormal ISOLATED THROMBOCYTOPENIA of idiopathic cause (primary)
-secondary: imm-mediated, assoc w/ SLE, HIV, HCV

  • acute: MC CHILDREN AFTER VIRUS
  • chronic: MC IN ADULTS (often recurs), F <40y, M >70y

Autoimmune Ab reaction vs platelets –> spleen destroys platelets (often after acute infection - virus)

  • sx- often asymptomatic, NO SPLENOMEGALY
  • INC MUCOCUTANEOUS BLEEDING: purpura, bruises, petechiae, epistaxis, menorrhagia, bleeding gums

-dx-
-ISOLATED THROMBOCYTOPENIA W/ NORMAL PT/PTT
(platelet disorder, not coagulation disorder)

  • tx- support/observe if >20K platelets and no bleed
  • children: OBSERVE –> IVIG
  • adults: CORTICOSTEROIDS –> IVIG –> splenectomy if refractory

*transfusion of platelets on if <20K to prevent spontaneous intracranial hemorrhage (only if bleeding after cortico + ivig)

31
Q

Hemophilia A (factor 8 deficiency)*

A

MC type hemophilia (80%)
X-linked recessive, MALES (female rare) or spont mutation
-first episode usually < 18yo

Lack of FACTOR 8 –> AFFECTS INTRINSIC PATHWAY –> failure to form hematomas

  • sx- (same as Hemo B)
  • HEMARTHROSIS (80%) +/- bleed in wt-bearing joints (mc ankle)
  • Excessive hemorrhage w/ trauma + surgery (incisional bleeding), nose bleeds, bruising, blood in stool/urine
  • less commonly present w/ purpura/petechiae (bc platelets are normal) or spontaneous hemorrhage
  • dx-
  • LOW FACTOR 8, PROLONGED PTT, normal platelets
  • tx-
  • FACTOR 8 INFUSION - to levels 25-100% prn
  • DESMOPRESSIN (DDAVP) - transiently increases Factor 8 and vWF release so may be used prior to procedures
32
Q

Hemophilia B (factor 9 deficiency) Christmas Disease*

A

X-linked recessive trait - MALES
Lack of FACTOR 9 –> AFFECTS INTRINSIC PATHWAY

  • sx- (same as Hemo A)
  • HEMARTHROSIS (80%) +/- bleed in wt-bearing joints
  • Excessive hemorrhage w/ trauma + surgery (incisional bleeding), nose bleeds, bruising, blood in stool/urine
  • less commonly present w/ purpura/petechiae (bc platelets are normal) or spontaneous hemorrhage
  • DEEP TISSUE BLEEDING
  • dx-
  • DEC FACTOR 9, PROLONGED PTT (BUT CORRECTS W/ MIXING STUDY)
  • tx-
  • FACTOR 9 INFUSION
  • DESMOPRESSIN NOT USEFUL!
  • -> MIXING STUDY
  • if affected blood is mixed w/normal plasma and PT/PTT corrects –> factor deficiency
  • IF DOESN’T CORRECT –> + PRESENCE OF FACTOR INHIBITORS (EX. LUPUS ANTICOAG, ANTIPHOSPHOLIPID SYNDROME)
33
Q

Von Willebrand Disease*

A

DEFICIENT/DEFECTIVE vWF –> INEFFECTIVE PLATELET ADHESION (aggregation normal)

  • vWF necessary for initial platelet adhesion and prevents Factor 8 degradation
  • autosomal dom disorder
  • MC HEREDITARY BLEEDING DISORDER (1% pop)
  • sx-
  • MUCOCUTANEOUS BLEEDING: easy bruising, epistaxis, gums, GI, periods; varing degrees
  • BLEED AFTER MINOR LACERATIONS > incisional bleed
  • PETECHIAE (rare in hemophilias)
  • dx-
  • DEC vWF LEVELS +/- PROLONGED PTT (dec Factor 8)
  • bleeding time and PTT worse w/ aspirin
  • stress, sx, pregnancy, OCP may inc vWF
  • DEC RISTOCETIN ACTIVITY TEST GOLD STANDARD (no platelet aggregation w/ ristocetin abx)
  • tx-
  • avoid aspirin, assess bleeding times before procedures
  • mild: no tx needed
  • mod: DESMOPRESSIN (DDAVP) inc vWF, Factor 8
  • sev: absent vWF –> supplement w/ vWF-containing products and Factor 8 (DDAVP NOT HELPFUL)
34
Q

hodgkin’s lymphoma*

A

Lymphocyte neoplasm

  • peaks @ 20yo and >50yo; MC in MALES
  • assoc w/ EBV
  • sx-
  • PAINLESS LYMPADENOPATHY - firm, nontender, mobile (esp upper body) ALCOHOL MAY INDUCE LYMPH NODE PAIN!
  • SYSTEMIC “B” SX: (advanced dz) PEL-EBSTEIN FEVER (cyclical fever 1-2 wks), NIGHT SWEATS, WT LOSS, anemia
  • dx-
  • EXCISIONAL BIOPSY –> REED-STERNBERG CELL PATHOGNOMONIC “OWL EYE” APPEARANCE
  • MEDIASTINAL LYMPHADENOPATHY - PET/CT scan to stg
  • tx-
  • local (stg 1,2,3a): radiation
  • stg 3b, 4: combo chemo
  • HODGKIN’S LYMPHOMA HIGHLY CURABLE COMPARED TO NON-HODGKINS
35
Q

non-hodgkin lymphoma*

A

Lymphocyte neoplasm: diffuse B cell, T cell, follicular

  • MC >50y; RF: INC AGE, IMMUNOSUPPRESSION
  • PERIPHERAL LYMPH NODES MC
  • sx-
  • PAINLESS LYMPHADENOPATHY –> EXTRANODAL SITES COMMON (GI, SKIN, CNS MC)
  • BURKITT LYMPHOMA - often presents w/ abd pain (sporadic), jaw involvement - histology “starry sky”
  • Systemic “B” sx: fever, night sweats, WL, anemia, pruritis rarer in NHL
  • dx- EXCISIONAL BX
  • PET/CT scan to stage
  • tx- UNPREDICTABLE COURSE
  • Follicular: indolent form (not usually curable) –> RITUXIMAB (AB vs CD20 on B cells)
  • Diffuse Large B Cell: MC and MOST AGGRESSIVE (but curable w/ chemo) R-CHOP
36
Q

waldenstrom macroglobulinemia

A

B-cell lymphoma –> PRODUCES EXCESS IgM

  • sx- often asymptomatic
  • ORGANOMEGALY:lymphadenopathy, hepatosplenomegaly
  • HYPERVISCOSITY SYNDROME (large IgM mol increase serum viscosity, slow blood through caps –> blurry vision, HA, vertigo, dizzy, diplopia, ataxia —> retinal hemorrhages
  • ANEMIA (bone marrow failure)
  • CHRONIC OOZING BLOOD FROM NOSE, GUMS (IgM interacts w/ platelets and inhibits fibrin formation)
  • peripheral neuropathy
  • CRYOGLOBULINEMIA - IgM precipitates out of serum in cold temps –> raynauds

-dx-
-SERUM PROTEIN ELECTROPHORESIS: IgM monoclonal spike (MM is IgG or IgA spike)
BM Biopsy: >10% lymphobplasmacytic infiltrate, DUTCHER BODIES

  • tx-
  • Responsive to chemo but rarely curative; CHOP may be used
  • Rituximab may be used alone if mild sx
  • PLASMAPHERESIS to treat severe hyperviscocity w/ comp
  • incurable but treatable - med survival rate 5 years
37
Q

monoclonal gammopathy of undetermined significance

A

INC IMMUNOGLOBULINS W/OUT CLINICAL SX/ORGAN DAMAGE

  • 1% adults; 3% >70yo - inc risk of devo MM or lymphoma
  • MC IgG (70%)
  • may be assoc w/ other dz, infx, auto imm

-sx- ASYMPTOMATIC BY DEFINITION

  • dx-
  • SERUM PROTEIN ELECTROPHORESIS: MONOCLONAL SPIKE (usually stable over time)
  • URINE PROTEIN ELECTROPHORESIS - none/stable amt bence-jones proteins
  • BM BIOPSY DEFINITIVE (<10% OF PLASMA CELLS)
  • absence of hyperCa, anemia, renal failure, lytic bone lesions (like MM)
  • tx-
  • CONSERVATIVE OR OBSERVATION - low malignant risk
38
Q

multiple myeloma (plasmacytoma)*

A

proliferation of SINGLE CLONE OF PLASMA CELLS –> INC MONOCLONAL AB (ESP IgG and IgA)
-RF: >65yo, AA, MEN

  • sx-
  • BONE PAIN: spine, ribs - due to OSTEOLYTIC LESIONS
  • RECURRENT INFX: strep pneumo, gram neg from LEUKOPENIA, hyperviscosity
  • HYPERCALCEMIA - bc of bone destruction
  • ANEMIA
  • KIDNEY FAILURE
  • dx-
  • Serum Electrophor: MONOCLONAL M SPIKE (IgG 60%)
  • Urine Electrophoresis: BENCE JONES PROTEINS
  • CBC: ROULEAUX FORMATION, inc ESR
  • xray: “PUNCHED OUT” LYTIC LESIONS
  • BM bx: PLASMACYTOSIS
  • tx-
  • AUTOLOGOUS STEM CELL TRANSPLANT DEFINITIVE
  • preceded by chemo
  • bisphosphonates for bony destruction
39
Q

acute lymphocytic leukemia (ALL)*

A

malignancy of lymphoid stem cells in BM –> lymph nodes, spleen, liver, other organs
-MC CHILDHOOD (peak 3-7yo); DOWN SYND >5yo

  • sx-
  • Pancytopenia sx: FEVER MC, fatigue, bone pain
  • CNS SX: ha, visual change, vomit
  • HEPATOSPLENOMEGALY, LYMPHADENOPATHY
  • petechiae, bruising
  • dx-
  • BM: HYPERCELLULAR W/ >20% BLASTS; WBC: 5-100K, thrombocytopenia

-tx-
-oral chemo; HIGHLY RESPONSIVE TO COMBO CHEMO
(remission >90%)
-stem cell transplant if relapse; METHOTREXATE FOR CNS DISEASE

40
Q

acute myelogenous leukemia (AML)*

A

-MC ACUTE FORM LEUKEMIA >50yo

-sx-
-PANCYTOPENIA, SPLENOMEGALY, GINGIVAL HYPERPLASIA
+/-LEUKOSTASIS (WBC >100K)

-dx-
>20% BLASTS (WBC)
-promyelocytic: +AUER RODS
-acute monocytic: gingival infiltration/hyperplasia
-MEGAKARYOCYTIC: INC IN DOWN SYNDROME
  • tx-
  • COMBO CHEMO, STEM CELL after remission
  • TUMOR LYSIS SYND: inc K, dec Ca, inc PHOS, hyperuricemia and renal failure –> ALLOPURINOL + FLUID
41
Q

chronic myelogenous leukemia (CML)*

A
  • well-differentiated WBC - granulocyte proliferation
  • OLDER MALES, >50y
  • sx-
  • asymptomatic until BLASTIC CRISIS (ACUTE), SPLENOMEGALY
  • dx-
  • PHILADELPHIA CHROM
  • WBC > 100K
  • chronic: <5% blasts
  • accelerated: 5-30% blasts
  • acute: >30% blasts
  • tx-
  • PO CHEMO, stem cell in servere/failed chemo
  • IMATINIB for PHILADELPHIA +
42
Q

chronic lymphocytic leukemia (CLL)*

A
  • B CELL CLONAL MALIGNANCY
  • MC LEUKEMIA IN ADULTS OVERALL
  • sx-
  • most asymptomatic (incidental finding of leukocytosis on routine labs)
  • FATIGUE MC, inc infx, lymphadenopathy, hepatosplenmeg
  • dx-
  • Peripheral Smear: SMUDGE CELLS (fragile B cells), WELL-DIFFERENTIATED LYMPHOCYTES
  • tx-
  • indolent: observe
  • SYMPTOMATIC OR PROGRESSIVE: CHEMO –> FLUDARABINE
  • stem cell transplant curative
  • ZAP-70+ –> poorer prognosis
43
Q

polycythemia vera (primary erythrocytosis)*

A

PRIMARY ERYTHROCYTOSIS = INC HCT W/OUT HYPOXIA

  • acquired myeloproliferative disorder w/ OVERPRODUCTION OF ALL 3 MYELOID CELL LINES (PRIMARILY RBC, but also WBC and platelets)
  • lymphocytes normal
  • MC MEN, PEAK 50-60y, caused by JAK2 MUTATION
  • sx-
  • DUE TO INC RBC: HYPERVISCOSITY OR THROMBOSIS
  • ha, dizzy, tinnitus, blurred vision, PRURITUS ESP AFTER HOT BATH, fatigue
  • ERYTHROMELALGIA: episodic burn/throb of hands/feet w/ edema
  • SPLENOMEGALY, FACIAL FLUSH, engorged retinal veins
  • SPENT PHASE: marrow fibrosis w/ marked pancytopenia
  • dx- all 3 major OR 1st 2 major + minor
  • MAJOR: INC RBC MASS (HGB/HCT), HYPERCELLULAR ON BM BX, JAK2 MUTATION
  • MINOR: DEC SERUM ERYTHROPOIETIN LEVELS
  • NORMAL O2 SAT, inc wbc, platelets, iron deficiency
  • tx-
  • PHLEBOTOMY MANAGEMENT OF CHOICE (until hct <45), low dose ASA
  • myelosuppresion: HYDROXYUREA
  • allopurinol if pt hyperuricemic
  • Ruxolitinib is a JAK inhibitor
44
Q

secondary erythrocytosis*

A

major cause of inc RBC mass; MC obese, hx of smoking

  • 3 major causes:
  • Reactive MC type: HYPOXIA, PULM DISEASE (COPD), high altitude, smokers
  • Pathologic: no underlying tissue hypoxia (renal dz –> Ca), fibroids, hepatoma
  • Relative Polycythemia: normal RBC mass in setting of dec plasma volume, dehydration
  • sx-
  • sx of underlying cause, cyanosis, clubbing, HTN, hepatosplenomegaly, +/- heart murmur

-dx-
-INC RBC/HCT W/ NORMAL WBC + PLATELETS –> distinguishes from polycythemia vera (1ry)
normal EPO levels

-tx- underlying disorder, smoking cessation

45
Q

hereditary hemochromatosis

A

EXCESS IRON DEPOSITION IN PARENCHYMAL CELLS OF HEART, LIVER, PANCREAS, ENDOCRINE ORGANS

  • auto recessive disorder of inc iron storage and inc iron absorption
  • Men MC, C282Y HFE GENOTYPE

-inc intestinal Fe absorption –> inc serum Fe and inc deposition into organs/glands; sx due to organ dysfx

  • sx-
  • may be asymptomatic in early stage, usually begin >40y
  • Liver: abd pain, CIRRHOSIS, fatigue, megaly, arthralgia
  • HF: CARDIOMYOPATHY, ARRHYTHMIAS, failure
  • Hypogonadism: teste atrophy and impotence
  • Pancreas: beta cell damage –> DM
  • METALLIC OR BRONZE SKIN –> “BRONZE DIABETES”

-dx-
-INC SERUM IRON (>200), INC TRANSFERRIN SAT, INC FERRITIN, dec TIBC (similar to lead poisoning)
+/- inc LFTs, genetic test for HFE gene, inc risk liver ca
-LIVER BIOPSY GOLD STANDARD –> INC HEMOSIDERIN

  • tx-
  • PHLEBOTOMY WEEKLY until depletion of iron –> maintenance 3-4x year for life
  • Chelating agents if unable to do phlebotomy (anemia)
  • Tx complications, test relatives, genetic counsel
  • NO ETOH or VIT C
46
Q

coagulopathy of advanced liver disease

A

ADVANCED LIVER DISEASE ASSOC W/ DECREASED PRODUCTION OF COAG FACTORS
-liver makes all except 8 and vWF

-etio: cirrhosis, ESLD, ETOH, hemochromatosis, hepatitis, ischemia

  • sx-
  • BLEEDING is the classic finding, esp GI
  • portal HTN –> splenomegaly –> thrombocytopenia
  • malabsorption of Vit K
  • dx-
  • INC PT (inc ptt as disease advances), corrects w/ mixing
  • LOW ALBUMIN
  • no response to vitamin K
  • P. Smear: +/-TARGET CELLS
  • tx-
  • FRESH FROZEN PLASMA w/ active bleeding or invasive procedure (to replace coag factors); vit K won’t correct
  • Cryoprecipitate if low fibrinogen
47
Q

factor 5 leiden mutation*

A

MC INHERITED CAUSE OF HYPERCOAGULABILITY (5%)

-mutated factor V RESISTANT to breakdown by activated PROTEIN C –> HYPERCOAGULABILITY –> INC DVT AND PE ESP IN YOUNG PATIENTS

  • dx-
  • activated protein C resistance assay; if pos, confirm w/ DNA test
  • normal PT/PTT
  • hepatic vein thrombosis; not assoc w/ inc MI or CVA
  • tx-
  • high risk –> indefinite anticoag (may need thromboprophylaxis during pregnancy to prevent miscarriages)
  • mod risk –> prophylaxis during high-risk procedures
48
Q

protein C deficiency

A

autosomal dominant - hypercoagulable disorder

  • PROTEIN C A VIT-K DEPENDENT ANTICOAG, made by liver, and stimulates fibrinolysis and clot lysis (inactivates factor 5 + 8)
  • increased risk of recurrent DVT and PE
  • sx-
  • RECURRENT DVT OR PULMONARY EMBOLI, +/- fam hx, 70% of clots spontaneous

-tx-
-Heparin –> PO ANTICOAG FOR LIFE
(may devo WARFARIN-INDUCED SKIN NECROSIS)

49
Q

antithrombin III deficiency

A

hypercoagulable disorder:

  • inherited: auto dom
  • acquired: liver dz, nephrotic syndrome, DIC, chemo
  • antithrombin III inactivates surplus throbin; activity potentiated by heparin
  • ANTITHROMBIN III DEF RESULTS IN VENOUS THROMBOSIS
  • sx-
  • RECURRENT DVT OR PE (1st episode btw 20-30y)
  • tx-
  • asymptomatic: treat w/ anticoag before surgical proc
  • w/ thrombotic event –> HIGH DOSE IV HEPARIN then oral anticoag indefinitely
50
Q

DVT*

A

Patient with a history of smoking, long-distance travel, surgery, oral contraceptives use
Complaining of unilateral leg edema, leg pain, tenderness, and warmth
Physical exam may show a positive Homan sign
Diagnosis is made by ultrasound; Gold standard is venography
Most commonly caused by stasis, hypercoagulable state, trauma (Virchow triad)
Treatment is anticoagulation
Warfarin is contraindicated in pregnancy
Comments: Risk stratification by Wells criteria

51
Q

Methemoglobinemia*

A

Fe3+ → Hb can’t bind O2
Leftward shift of oxyhemoglobin dissociation curve
Causes: dapsone, nitrates, antimalarials, “-aines” (benzocaine)

sx:
SOB + clear lungs on PE + normal CXR
Cyanosis
Brown blood
Pulse ox in high 80s, will not respond to O2

dx: Co-oximetry

Tx: Methylene blue

52
Q

Heparin-Induced Thrombocytopenia (HIT)*

A

Patient with a history of recently starting heparin
Labs will show a 50% decrease in platelets
Treatment is to stop heparin, use direct thrombin inhibitor
Type 1: PLT recovery with or without heparin cessation
Type 2: autoimmune, venous/arterial thromboses

53
Q

fanconi anemia*

A

most common form of inherited aplastic anemia
PE will show absent or hypoplastic thumb, short stature, low set ears, deafness, strabismus, skin hyper- or hypopigmentation, cafe-au-lait spots, renal abnormalities
Labs will show macrocytic anemia and elevated fetal hemoglobin (HgF)
Most commonly caused by autosomal recessive defect in DNA repair
Treatment is bone marrow transplant
Comments: Most common form of inherited aplastic anemia. Increased risk for AML, solid tumors and aplastic anemia

54
Q

Antiphospholipid Antibody Syndrome*

A

Patient with a history of lupus or other rheumatic diseases
Complaining of repeated spontaneous abortions
Labs will show thrombocytopenia
Most commonly caused by autoimmune
Treatment is anti-coagulation

Concepts / Lists (16 decks)

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