Transcript HEREDITARY/ACQUIRED ANEMIA

HEREDITARY/ACQUIRED
ANEMIA
DR. BATIZY, D.O.
PREPARED BY JEFFREY L PAY, D.O.
NOVEMBER 3, 2003
HEREDITARY HEMOLYTIC
ANEMIA
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CHARACTERIZED BY:
- DEFECTS OF HEMOGLOBIN OR
- DEFECTS OF THE RBC MEMBRANE
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RESULTS IN PREMATURE
DESTRUCTION OF RED CELLS
TYPES OF HA
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SICKLE CELL DISEASE
THALASSEMIAS
G6PD DEFICIENCY
HEREDITARY SPHEROCYTOSIS
SICKLE CELL DISEASE
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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
SICKLE CELL ANEMIA
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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
SCD - PATHOPHYS
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HEMOGLOBIN S CAUSED BY MUTATION
OF ß CHAIN; substitution of the AA valine for
glutamine at position 6 of the β-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
SCD – CLINICAL SX
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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
SCD – CLINICAL SX
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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
SCD – CAUSES OF
VASO-OCCLUSIVE CRISES
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COLD EXPOSURE, DEHYDRATION,
HIGH ALTITUDE
INFECTIONS (ENCAPSULATED – H.
influenza & PNEUMOCOCCI
SCD – DIAGNOSIS
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SCD USUALLY DX EARLY IN PT LIFE
PRESCENCE OF SICKLING RBC’S 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
SCD – DIFF DX
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OSTEOMYELITIS
ACUTE ARTHRITIS
PANCREATITIS
HEPATITIS
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PE
MENINGITIS
PID
PYELONEPHRITIS
SCD – ER TREATMENT
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PTS WITH DEHYDRATION OR ACUTE PAIN
REHYDRATED ORALLY OR WITH IV
FLUIDS NORMAL SALINE @ 1.5 TIMES
MAINTENANCE
NARCOTICS PROMPTLY FOR SEVERE
PAIN, BEWARE OF DRUG SEEKERS
INFECTION OR TEMP > 38C HAVE
CULTURES DRAWN; START BROAD-SPEC
ABX: CEFUROXIME OR CEFTRIAXONE
SCD – ER TREATMENT
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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
SCD – ER TREATMENT
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PTS WITH ACUTE BONE PAIN –
THINK OSTEOMYELITIS
DRAW CULTURES AND START IV ABX
COVERING Staph aureus and Salmonella
typhimurium
SCD – ADMIT/DISPO
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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 >38C OR
WORSENING SX
THALASSEMIAS
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MICROCYTIC, HYPOCHROMIC,
HEMOLYTIC ANEMIA
MOST COMMON IN AFRICAN,
MEDITERRANEAN, MIDDLE
EASTERN, & SOUTHEAST ASIAN
DESCENT
MULTIPLE VARIANTS
THALASSEMIAS
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CHARACTERIZED BY DEFECTIVE
SYNTHESIS OF GLOBIN CHAINS,
UNABLE TO PRODUCE NORMAL
ADULT HEMOGLOBIN
TRAIT THOUGHT TO BE PROTECTIVE
AGAINST MALARIA AS WELL
HEMOGLOBIN
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NORMAL ADULT RBC CONSISTS OF 3
FORMS OF Hb:
- HbA - 2 α and 2 β globin chains
- HbA2 – 2 α and 2 δ globin chains
- HbF - 2 α and 2 γ globin chains
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THALASSEMIAS α and β
THALASSEMIAS
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TYPES OF DZ CHARACTERIZED BY
DEFFERING EXTREMES OF ANEMIA
DEPENDS ON AMOUNT OF
INEFFECTIVE ERYTHROPOIESIS AND
PREMATURE DESTRUCTION OF
CIRCULATING RBC’S
HYPOXIA IN SEVERE CASES
G6PD DEFICIENCY
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MOST COMMON HUMAN ENZYME
DEFECT
X-LINKED DISORDER
AFFECTS 15% OF U.S. BLACK MALES
DECREASE IN GLUTATHIONE
LEVELS
G6PD DEFICIENCY
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HEINZ BODIES SEEN ON
PERIPHERAL BLOOD SMEAR
NEONATAL JAUNDICE 1-4 DAYS
AFTER BIRTH IN SEVERE VARIANTS
INCREASE INCIDENCE OF
PIDMENTED GALLSTONES AND
SPLENOMEGALY
G6PD DEFICIENCY
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ACUTE HEMOLYTIC CRISIS DUE TO:
- BACTERIAL/VIRAL INFECTION
- OXIDANT DRUGS (SULFAMETHOXAZOLE)
- METABOLIC ACIDOSIS (DKA)
- RENAL FAILURE
- INGESTION OF FAVA BEANS
G6PD DEFICIENCY
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DIAGNOSIS – QUANTITATIVE ASSAY
DETECTING LOW ENZYME
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TREATMENT – SUPPORTIVE AND
PREVENTATIVE
HEREDITARY SPHEROCYTOSIS
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RBS MEMBRANE DEFECT
MOST COMMON HEREDITARY
ANEMIA FROM PTS OF NORTHERN
EUROPEAN DESCENT
AUTOSOMAL DOMINANT
MUTATIONS IN SPECTRIN AND
ANKYRIN (MEMBRANE PROTEINS)
HEREDITARY SPHEROCYTOSIS
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SPHEROCYTES – IN PERIPHERAL
BLOOD SMEAR
SPHEROCYTES UNABLE TO PASS
THROUGH THE SPLEEN
SEVERE CASES REQUIRE A
SPLENECTOMY
HEREDITARY SPHEROCYTOSIS
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NEONATAL JAUNDICE IN 1ST WEEK
OCCURS IN 30-50% OF HS PTS
ANEMIA, SPLENOMEGALY,
JAUNDICE, AND TRANSFUSIONS
NEEDED VARY DEPENDING ON
SEVERITY OF DZ
ACQUIRED HEMOLYTIC ANEMIA
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DESTRUCTION OF RBC’S NO DUE TO
GENETIC/CONGENITAL DISORDER
OF HGB SYNTHESIS OR RBC
MEMBRANE
AUTOIMMUNE, ALLOIMMUNE,
DRUG-RELATED CAUSES
MICROANGIOPATHIC SYNDROMES
(TTP, HUS)
AUTOIMMUNE HA
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PTS MAKE ANITBODIES AGAINST
THEIR OWN RBC’S
WARM-TYPE AIHA – 70% CASES
- IgG MEDIATED
COLD-TYPE AIHA – IgM MEDIATED
- 2 SUBTYPES
DRUG RELATED HA
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ALPHAMETHYLDOPA
LEVODOPA
PROCAINAMIDE
SULFA DRUGS
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PENICILLIN
CEFTRIAXONE
CEFOTETAN
QUINIDINE
ALLOIMMUNE HA
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HEMOLYTIC DZ OF NEWBORN
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HEMOLYTIC TRANSFUSION
REACTIONS
ALLOIMMUNE HA - NEWBORN
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MATERNAL ALLOANTIBODIES FORM
AFTER RhD-NEGATIVE MATERNAL
RBC’S EXPOSED TO RhD-POSITIVE
FETAL BLOOD
ABS CROSS PLACENTA AND
DESTROY FETAL RBC’S
- ANEMIA, FETAL HYDROPS, DEATH,
JAUNDICE
ALLOIMMUNE HA - TRANSFUSION
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PT HAS PREVIOUS TRANSFUSION
SENSITIZATION TO ALLOGENIC RBC
ANTIGEN OCCURS
LATER TRANSFUSIONS, PT MAY
DEVELOP FEVER, CP, TACHYPNEA,
TACHYCARDIA, HYPOTENSION,
HEMOGLOBINURIA, OLIGURIA
MICROANGIOPATHIC SYNDROMES
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THROMBOCYTOPENIC PURPURA
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HEMOLYTIC UREMIC SYNDROME
TTP & HUS - PATHOPHYS
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PLATELET AGGREGATION IN THE
MICROVASCULATURE CIRCULATION
VIA MEDIATION OF von
WILLEBRAND’S FACTOR LEADS TO
THROMBOCYTOPENIA AND
FRAGMENTATION OF RBC’S AS THEY
PASS THROUGH THESE OCCLUDED
ARTERIOLES AND CAPILLARIES
THROMBOCYTOPENIC PURPURA (TTP)
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PLATLET COUNTS < 20,000
MORE COMMON IN WOMEN AGES
10-60
FEVER, NEUROLOGIC DEFICITS,
HEMORRAGE, AND RENAL
INSUFFICIENCY
UNTREATED – 80-90% MORTALITY
TTP
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SCHISTOCYTES OR HELMET CELLS
SEEN OF PERIPHERAL SMEAR
INCREASED BUN/Cr LEVELS
TTP
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PREGNANCY IS THE MOST COMMON
PRECIPITATING EVENT FOR TTP
PREECLAMPSIA SIMILAR TO TTP;
DELIVERY TX FOR PREECLAMPSIA,
NOT CURE TTP
TTP – ER TREATMENT
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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
TTP – ER TREATMENT
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PT MAY NEED SPLENECTOMY
AZATHIOPRINE AND
CYCLOPHOSPHAMIDE FOR THOSE
WHO FAIL OR CANNOT TOLERATE
STEROIDS
HUS
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DZ OF EARLY CHILDHOOD
PEAK INCIDENCE BETWEEN 6mo-4yr
OFTEN FOLLOWS BACTERIAL/VIRAL
ILLNESS
MORTALILY 5-15%, WORSE IN OLDER
CHILDREN & ADULTS
HUS
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CHARACTERIZED BY
-ACUTE RENAL FAILURE
-MICROANGIOPATHIC HA
-FEVER
-THROMBOCYTOPENIA (NOT AS
SEVERE AS TTP)
HUS
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THE MOST COMMON CAUSE OF
ACUTE RENAL FAILURE IN
CHILDHOOD
E.Coli O157:H7 COMMON CAUSE
MICROTHORMBI ARE CONFINED
MAINLY TO KIDENYS, WHERE TTP
MORE WIDESPREAD
HUS – ER TREATMENT
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MILD HUS < 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
HELLP SYNDROME
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HEMOLYSIS
ELEVATED LIVER ENZYMES
LOW PLATLET COUNTS
HELLP SYNDROME
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1 IN 1OOO PREGNANCIES
SEEN IN PRESENCE OF ECLAMPSIA,
PREECLAMPSIA, AND PLACENTAL
ABRUPTION
MAY EXTEND UP TO 6 DAYS
POSTPARTUM
HELLP SYNDROME
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RUQ AND EPIGASTRIC PAIN – SEEN
IN 90% OF PTS (POSSIBLE HEPATIC
RUPTURE)
DX BASED ON LAB DATA
DECREASED SERUM HAPTOGLOBIN
LEVEL MOST SENSITIVE
HELLP SYNDROME - TX
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PROMPT DELIVERY OF INFANT
SUPPORTIVE CARE FOR SEIZURES
AND HTN CRISIS
STEROIDS MAY HELP FETAL LUNGS,
BUT NO BENEFIT TO HELLP
SYNDROME
THE END
QUESTIONS????
1. PT WITH SICKLE CELL
DISEASE ARE AT RISK FOR
SERIOUS INFECTIONS BY WHICH?
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A)
B)
C)
D)
CAPSULATED ORGANISMS
ENCAPSULATED ORGANISMS
BOTH A & B
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
3. G6PD DEFICIENCY RESULTS IN A
LOW LEVEL OF WHICH ENZYME?
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A)
B)
C)
D)
FOLIC ACID
GLUTATHIONE
SPHINGOMYELIN
B12
4. WHICH OF THE FOLLOWING
STATEMENTS IS TRUE?
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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
5) WHICH OF THE FOLLOWING IS
NOT PART OF THE HELLP
SYNDROME?
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A)
B)
C)
D)
E)
HIGH BUN/CR
LOW PLATELETS
ELEVATED LIVER ENZYMES
HEMOLYSIS
THROMBOCYTOPENIA