HEREDITARY/ACQUIRED ANEMIA

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HEREDITARY/ACQUIRED ANEMIA

• DR. BATIZY, D.O.
• PREPARED BY JEFFREY L PAY, D.O.
• NOVEMBER 3, 2003

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HEREDITARY HEMOLYTIC ANEMIA

• CHARACTERIZED BY
  - DEFECTS OF HEMOGLOBIN OR
  - DEFECTS OF THE RBC MEMBRANE
• RESULTS IN PREMATURE DESTRUCTION OF RED CELLS

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TYPES OF HA

• SICKLE CELL DISEASE
• THALASSEMIAS
• G6PD DEFICIENCY
• HEREDITARY SPHEROCYTOSIS

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SICKLE CELL DISEASE

• INHERITED, AUTOSOMAL RECESSIVE TRAIT DISEASE
  SEEN IN PTS WHO ARE HOMOZYGOUS FOR THE SICKLE
  CELL GENE (HbSS)
• MOST COMMON REASON TO ER PAINFUL VASO-OCCLUSIVE
  CRISIS
• ACUTE CHEST SYNDROME (ACS) LEADING CAUSE OF DEATH
  FROM SCD IN US

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SICKLE CELL ANEMIA

• SICKLE CELL TRAIT IN 8 OF THE U.S. BLACK
  POPULATION
• PEOPLE WITH TRAIT HAVE A NORMAL LIFE SPAN AND
  USUALLY ASYMPTOMATIC
• SICKLE CELL TRAIT THOUGHT TO BE PROTECTIVE
  AGAINST MALARIA

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SCD - PATHOPHYS

• HEMOGLOBIN S CAUSED BY MUTATION OF ß CHAIN
  substitution of the AA valine for glutamine at
  position 6 of the ß-globin chain
• DEOXYGENATED HEMOGLOBIN S POLYMERIZES, WHICH
  DEFORMS RBC AND CAUSES SICKLED APPEARANCE
• SICKLED CELL INCREASES VISCOSITY OF BLOOD,
  OBSTRUCTS MICROVASC
• VASO-OCCLUSIVE CRISIS OCCURS FROM SICKLING IN
  MICROCIRCULATION

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SCD CLINICAL SX

• PTS ARE FUNCTIONALLY ASPLENIC AFTER EARLY
  CHILDHOOD, AT RISK FOR SERIOIUS INFECTION FROM
  ENCAPSULATED ORGANISMS
• PTS MAY HAVE CHF, CM, COR PULMONALE, LE
  ULCERATIONS, ICTERUS, HEPATOMEGALY
• PTS WITH ACS WILL HAVE PULMONARY SX PLEURITIC
  CP, FEVER, HYPOXIA

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SCD CLINICAL SX

• NEUROLOGIC SX CEREBRAL INFARCT IN KIDS,
  HEMORRAGE IN ADULTS TIA, SEIZURES, HA, COMA
• PRIAPISM
• SWELLING OF HANDS FEET DUE TO VASO-OCCLUSION
• INFARCTION OF RENAL MEDULLA, ASSOC WITH FLANK
  PAIN AND HEMATURIA

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SCD CAUSES OF VASO-OCCLUSIVE CRISES

• COLD EXPOSURE, DEHYDRATION, HIGH ALTITUDE
• INFECTIONS (ENCAPSULATED H. influenza
  PNEUMOCOCCI

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SCD DIAGNOSIS

• SCD USUALLY DX EARLY IN PT LIFE
• PRESCENCE OF SICKLING RBCS ON PERIPHERAL BLOOD
  SMEAR IS DX
• DROP IN HBG BY 2 g/dL FROM BASELINE SUGGESTS
  ACUTE APLASTIC CRISIS
• RETIC COUNT COUNT LESS THAN BASELINE OF 5-15
  MAY REFLECT APLASTIC CRISIS
• LEUKOCYTOSIS WITH LEFT SHIFT INFECTION MAYBE
  CAUSE OF CRISIS

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SCD DIFF DX

• OSTEOMYELITIS
• ACUTE ARTHRITIS
• PANCREATITIS
• HEPATITIS

• PE
• MENINGITIS
• PID
• PYELONEPHRITIS

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SCD ER TREATMENT

• PTS WITH DEHYDRATION OR ACUTE PAIN REHYDRATED
  ORALLY OR WITH IV FLUIDS NORMAL SALINE _at_ 1.5
  TIMES MAINTENANCE
• NARCOTICS PROMPTLY FOR SEVERE PAIN, BEWARE OF
  DRUG SEEKERS
• INFECTION OR TEMP gt 38C HAVE CULTURES DRAWN
  START BROAD-SPEC ABX CEFUROXIME OR CEFTRIAXONE

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SCD ER TREATMENT

• TRANSFUSION FOR SC CRISIS OR COMPLICATIONS IS
  RESERVED FOR SPECIFIC INDICATIONS APLASTIC
  CRISIS, PREGNANCY, STROKE, RESP FAILURE, SURGERY,
  PRIAPISM
• PTS WITH PRIAPISM NEED HYDRATION, ANALGESIA, AND
  IMMEDIATE UROLOGY CONSULT

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SCD ER TREATMENT

• PTS WITH ACUTE BONE PAIN THINK OSTEOMYELITIS
• DRAW CULTURES AND START IV ABX COVERING Staph
  aureus and Salmonella typhimurium

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SCD ADMIT/DISPO

• ADMISSION CRITERIA INCLUDE PULM, NEURO, APLASTIC,
  OR INFECTIOUS CRISES SPLENIC SEQUESTRATION
  INTRACTIBLE PAIN PERSISTENT N/V OR UNCERTAIN DX
• DISCHARGED PTS SHOULD RECEIVE ORAL ANALGESICS,
  CLOSE FOLLOW UP, AND INSTRUCTIONS TO RETURN TO ER
  IMMEDIATELY FOR FEVER gt38C OR WORSENING SX

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THALASSEMIAS

• MICROCYTIC, HYPOCHROMIC, HEMOLYTIC ANEMIA
• MOST COMMON IN AFRICAN, MEDITERRANEAN, MIDDLE
  EASTERN, SOUTHEAST ASIAN DESCENT
• MULTIPLE VARIANTS

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THALASSEMIAS

• CHARACTERIZED BY DEFECTIVE SYNTHESIS OF GLOBIN
  CHAINS, UNABLE TO PRODUCE NORMAL ADULT HEMOGLOBIN
• TRAIT THOUGHT TO BE PROTECTIVE AGAINST MALARIA AS
  WELL

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HEMOGLOBIN

• NORMAL ADULT RBC CONSISTS OF 3 FORMS OF Hb
  - HbA
  - 2 a and 2 ß globin chains
  - HbA2 2 a and 2 d globin chains
  - HbF - 2 a and 2 ? globin chains
• THALASSEMIAS a and ß

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THALASSEMIAS

• TYPES OF DZ CHARACTERIZED BY DEFFERING EXTREMES
  OF ANEMIA
• DEPENDS ON AMOUNT OF INEFFECTIVE ERYTHROPOIESIS
  AND PREMATURE DESTRUCTION OF CIRCULATING RBCS
• HYPOXIA IN SEVERE CASES

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G6PD DEFICIENCY

• MOST COMMON HUMAN ENZYME DEFECT
• X-LINKED DISORDER
• AFFECTS 15 OF U.S. BLACK MALES
• DECREASE IN GLUTATHIONE LEVELS

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G6PD DEFICIENCY

• HEINZ BODIES SEEN ON PERIPHERAL BLOOD SMEAR
• NEONATAL JAUNDICE 1-4 DAYS AFTER BIRTH IN SEVERE
  VARIANTS
• INCREASE INCIDENCE OF PIDMENTED GALLSTONES AND
  SPLENOMEGALY

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G6PD DEFICIENCY

• ACUTE HEMOLYTIC CRISIS DUE TO -
  BACTERIAL/VIRAL INFECTION - OXIDANT
  DRUGS (SULFAMETHOXAZOLE) -
  METABOLIC ACIDOSIS (DKA) -
  RENAL FAILURE
  - INGESTION OF FAVA BEANS

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G6PD DEFICIENCY

• DIAGNOSIS QUANTITATIVE ASSAY DETECTING LOW
  ENZYME
• TREATMENT SUPPORTIVE AND PREVENTATIVE

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HEREDITARY SPHEROCYTOSIS

• RBS MEMBRANE DEFECT
• MOST COMMON HEREDITARY ANEMIA FROM PTS OF
  NORTHERN EUROPEAN DESCENT
• AUTOSOMAL DOMINANT
• MUTATIONS IN SPECTRIN AND ANKYRIN (MEMBRANE
  PROTEINS)

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HEREDITARY SPHEROCYTOSIS

• SPHEROCYTES IN PERIPHERAL BLOOD SMEAR
• SPHEROCYTES UNABLE TO PASS THROUGH THE SPLEEN
• SEVERE CASES REQUIRE A SPLENECTOMY

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HEREDITARY SPHEROCYTOSIS

• NEONATAL JAUNDICE IN 1ST WEEK OCCURS IN 30-50 OF
  HS PTS
• ANEMIA, SPLENOMEGALY, JAUNDICE, AND TRANSFUSIONS
  NEEDED VARY DEPENDING ON SEVERITY OF DZ

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ACQUIRED HEMOLYTIC ANEMIA

• DESTRUCTION OF RBCS NO DUE TO GENETIC/CONGENITAL
  DISORDER OF HGB SYNTHESIS OR RBC MEMBRANE
• AUTOIMMUNE, ALLOIMMUNE, DRUG-RELATED CAUSES
• MICROANGIOPATHIC SYNDROMES (TTP, HUS)

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AUTOIMMUNE HA

• PTS MAKE ANITBODIES AGAINST THEIR OWN RBCS
• WARM-TYPE AIHA 70 CASES - IgG
  MEDIATED
• COLD-TYPE AIHA IgM MEDIATED - 2
  SUBTYPES

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DRUG RELATED HA

• ALPHA-METHYLDOPA
• LEVODOPA
• PROCAINAMIDE
• SULFA DRUGS

• PENICILLIN
• CEFTRIAXONE
• CEFOTETAN
• QUINIDINE

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ALLOIMMUNE HA

• HEMOLYTIC DZ OF NEWBORN
• HEMOLYTIC TRANSFUSION REACTIONS

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ALLOIMMUNE HA - NEWBORN

• MATERNAL ALLOANTIBODIES FORM AFTER RhD-NEGATIVE
  MATERNAL RBCS EXPOSED TO RhD-POSITIVE FETAL
  BLOOD
• ABS CROSS PLACENTA AND DESTROY FETAL RBCS
  - ANEMIA, FETAL HYDROPS,
  DEATH,
  JAUNDICE

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ALLOIMMUNE HA - TRANSFUSION

• PT HAS PREVIOUS TRANSFUSION
• SENSITIZATION TO ALLOGENIC RBC ANTIGEN OCCURS
• LATER TRANSFUSIONS, PT MAY DEVELOP FEVER, CP,
  TACHYPNEA, TACHYCARDIA, HYPOTENSION,
  HEMOGLOBINURIA, OLIGURIA

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MICROANGIOPATHIC SYNDROMES

• THROMBOCYTOPENIC PURPURA
• HEMOLYTIC UREMIC SYNDROME

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TTP HUS - PATHOPHYS

• PLATELET AGGREGATION IN THE MICROVASCULATURE
  CIRCULATION VIA MEDIATION OF von WILLEBRANDS
  FACTOR LEADS TO THROMBOCYTOPENIA AND
  FRAGMENTATION OF RBCS AS THEY PASS THROUGH THESE
  OCCLUDED ARTERIOLES AND CAPILLARIES

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THROMBOCYTOPENIC PURPURA (TTP)

• PLATLET COUNTS lt 20,000
• MORE COMMON IN WOMEN AGES 10-60
• FEVER, NEUROLOGIC DEFICITS, HEMORRAGE, AND RENAL
  INSUFFICIENCY
• UNTREATED 80-90 MORTALITY

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TTP

• SCHISTOCYTES OR HELMET CELLS SEEN OF PERIPHERAL
  SMEAR
• INCREASED BUN/Cr LEVELS

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TTP

• PREGNANCY IS THE MOST COMMON PRECIPITATING EVENT
  FOR TTP
• PREECLAMPSIA SIMILAR TO TTP DELIVERY TX FOR
  PREECLAMPSIA, NOT CURE TTP

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TTP ER TREATMENT

• PREDNISONE 1-2mg/kg/day INITIALLY
• PLASMA EXCHANGE TRANSFUSION IS FOUNDATION FOR TX
  (INFUSE FRESH FROZEN PLASMA IF TRANSFUSION
  UNAVAILABLE
• AVOID PLATELET TRANSFUSION
• NEVER USE ASPIRIN

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TTP ER TREATMENT

• PT MAY NEED SPLENECTOMY
• AZATHIOPRINE AND CYCLOPHOSPHAMIDE FOR THOSE WHO
  FAIL OR CANNOT TOLERATE STEROIDS

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HUS

• DZ OF EARLY CHILDHOOD
• PEAK INCIDENCE BETWEEN 6mo-4yr
• OFTEN FOLLOWS BACTERIAL/VIRAL ILLNESS
• MORTALILY 5-15, WORSE IN OLDER CHILDREN ADULTS

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HUS

• CHARACTERIZED BY
  -ACUTE RENAL FAILURE -MICROANGIOPATHIC HA
  -FEVER
  
  -THROMBOCYTOPENIA (NOT AS
  SEVERE AS TTP)

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HUS

• THE MOST COMMON CAUSE OF ACUTE RENAL FAILURE IN
  CHILDHOOD
• E.Coli O157H7 COMMON CAUSE
• MICROTHORMBI ARE CONFINED MAINLY TO KIDENYS,
  WHERE TTP MORE WIDESPREAD

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HUS ER TREATMENT

• MILD HUS lt 24hr OF URINARY SX NEELS ONLY
  FLUID/ELECTROLYTE CORRECTION AND SUPPORT CARE
• STEROID THERAPY
• HEMODIAYLSIS IF ACUTE RENAL FAILURE PRESENT
• ABX TX CONTROVERSIAL WHEN E.Coli PRESNENT DO NOT
  USE ANTIMOLITY DRUG, INCREASE RISK OF DEVELOP HUS

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HELLP SYNDROME

• HEMOLYSIS
• ELEVATED LIVER ENZYMES
• LOW PLATLET COUNTS

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HELLP SYNDROME

• 1 IN 1OOO PREGNANCIES
• SEEN IN PRESENCE OF ECLAMPSIA, PREECLAMPSIA, AND
  PLACENTAL ABRUPTION
• MAY EXTEND UP TO 6 DAYS POSTPARTUM

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HELLP SYNDROME

• RUQ AND EPIGASTRIC PAIN SEEN IN 90 OF PTS
  (POSSIBLE HEPATIC RUPTURE)
• DX BASED ON LAB DATA
• DECREASED SERUM HAPTOGLOBIN LEVEL MOST SENSITIVE

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HELLP SYNDROME - TX

• PROMPT DELIVERY OF INFANT
• SUPPORTIVE CARE FOR SEIZURES AND HTN CRISIS
• STEROIDS MAY HELP FETAL LUNGS, BUT NO BENEFIT TO
  HELLP SYNDROME

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THE END

• QUESTIONS????

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1. PT WITH SICKLE CELL DISEASE ARE AT RISK FOR
SERIOUS INFECTIONS BY WHICH?

• A) CAPSULATED ORGANISMS
• B) ENCAPSULATED ORGANISMS
• C) BOTH A B
• D) NEITHER A OR B

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• T OR F
• 2. PT WITH THE SICKLE CELL TRAIT ARE OFTEN
  SYMPTOMATIC AND WILL NEED A SPLENECTOMY

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3. G6PD DEFICIENCY RESULTS IN A LOW LEVEL OF
WHICH ENZYME?

• A) FOLIC ACID
• B) GLUTATHIONE
• C) SPHINGOMYELIN
• D) B12

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4. WHICH OF THE FOLLOWING STATEMENTS IS TRUE?

• A) TTP IS MORE COMMON IN MEN 20-40 YEARS OF AGE
• B) TTP HAS NORMAL PLATELET LEVELS
• C) HUS DOES NOT USUALLY AFFECT THE KIDNEYS
• D) HUS IS DISEASE OF THE YOUNG, USUALLY 6MO-4YRS
  OF AGE

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5) WHICH OF THE FOLLOWING IS NOT PART OF THE
HELLP SYNDROME?

• A) HIGH BUN/CR
• B) LOW PLATELETS
• C) ELEVATED LIVER ENZYMES
• D) HEMOLYSIS
• E) THROMBOCYTOPENIA