HEREDITARY/ACQUIRED ANEMIA

DR. BATIZY, D.O. PREPARED BY JEFFREY L PAY, D.O.

NOVEMBER 3, 2003

HEREDITARY HEMOLYTIC ANEMIA CHARACTERIZED BY:

- DEFECTS OF HEMOGLOBIN OR - DEFECTS OF THE RBC MEMBRANE

RESULTS IN PREMATURE DESTRUCTION OF RED CELLS

TYPES OF HA SICKLE CELL DISEASE THALASSEMIAS G6PD DEFICIENCY HEREDITARY SPHEROCYTOSIS

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

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

SCD - PATHOPHYS 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 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 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 COLD EXPOSURE, DEHYDRATION,

HIGH ALTITUDE INFECTIONS (ENCAPSULATED – H.

influenza & PNEUMOCOCCI

SCD – DIAGNOSIS 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 OSTEOMYELITIS ACUTE ARTHRITIS PANCREATITIS HEPATITIS

PE MENINGITIS PID PYELONEPHRITIS

SCD – ER TREATMENT 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 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 PTS WITH ACUTE BONE PAIN –

THINK OSTEOMYELITIS DRAW CULTURES AND START IV

ABX COVERING Staph aureus and Salmonella typhimurium

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 >38C OR WORSENING SX

THALASSEMIAS MICROCYTIC, HYPOCHROMIC,

HEMOLYTIC ANEMIA MOST COMMON IN AFRICAN,

MEDITERRANEAN, MIDDLE EASTERN, & SOUTHEAST ASIAN DESCENT

MULTIPLE VARIANTS

THALASSEMIAS CHARACTERIZED BY DEFECTIVE

SYNTHESIS OF GLOBIN CHAINS, UNABLE TO PRODUCE NORMAL ADULT HEMOGLOBIN

TRAIT THOUGHT TO BE PROTECTIVE AGAINST MALARIA AS WELL

HEMOGLOBIN 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

THALASSEMIAS α and β

THALASSEMIAS 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 MOST COMMON HUMAN ENZYME

DEFECT X-LINKED DISORDER AFFECTS 15% OF U.S. BLACK MALES DECREASE IN GLUTATHIONE

LEVELS

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

G6PD DEFICIENCY ACUTE HEMOLYTIC CRISIS DUE TO:

- BACTERIAL/VIRAL INFECTION - OXIDANT DRUGS

(SULFAMETHOXAZOLE) - METABOLIC ACIDOSIS (DKA) - RENAL FAILURE - INGESTION OF FAVA BEANS

G6PD DEFICIENCY DIAGNOSIS – QUANTITATIVE ASSAY

DETECTING LOW ENZYME

TREATMENT – SUPPORTIVE AND PREVENTATIVE

HEREDITARY SPHEROCYTOSIS RBS MEMBRANE DEFECT MOST COMMON HEREDITARY

ANEMIA FROM PTS OF NORTHERN EUROPEAN DESCENT

AUTOSOMAL DOMINANT MUTATIONS IN SPECTRIN AND

ANKYRIN (MEMBRANE PROTEINS)

HEREDITARY SPHEROCYTOSIS SPHEROCYTES – IN PERIPHERAL

BLOOD SMEAR SPHEROCYTES UNABLE TO PASS

THROUGH THE SPLEEN SEVERE CASES REQUIRE A

SPLENECTOMY

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

ACQUIRED HEMOLYTIC ANEMIA 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 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 ALPHA-

METHYLDOPA LEVODOPA PROCAINAMIDE SULFA DRUGS

PENICILLIN CEFTRIAXONE CEFOTETAN QUINIDINE

ALLOIMMUNE HA HEMOLYTIC DZ OF NEWBORN

HEMOLYTIC TRANSFUSION REACTIONS

ALLOIMMUNE HA - NEWBORN 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 PT HAS PREVIOUS TRANSFUSION SENSITIZATION TO ALLOGENIC RBC

ANTIGEN OCCURS LATER TRANSFUSIONS, PT MAY

DEVELOP FEVER, CP, TACHYPNEA, TACHYCARDIA, HYPOTENSION, HEMOGLOBINURIA, OLIGURIA

MICROANGIOPATHIC SYNDROMES THROMBOCYTOPENIC PURPURA

HEMOLYTIC UREMIC SYNDROME

TTP & HUS - PATHOPHYS 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)

PLATLET COUNTS < 20,000 MORE COMMON IN WOMEN AGES

10-60 FEVER, NEUROLOGIC DEFICITS,

HEMORRAGE, AND RENAL INSUFFICIENCY

UNTREATED – 80-90% MORTALITY

TTP SCHISTOCYTES OR HELMET CELLS

SEEN OF PERIPHERAL SMEAR INCREASED BUN/Cr LEVELS

TTP PREGNANCY IS THE MOST COMMON

PRECIPITATING EVENT FOR TTP PREECLAMPSIA SIMILAR TO TTP;

DELIVERY TX FOR PREECLAMPSIA, NOT CURE TTP

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

TTP – ER TREATMENT PT MAY NEED SPLENECTOMY AZATHIOPRINE AND

CYCLOPHOSPHAMIDE FOR THOSE WHO FAIL OR CANNOT TOLERATE STEROIDS

HUS DZ OF EARLY CHILDHOOD PEAK INCIDENCE BETWEEN 6mo-4yr OFTEN FOLLOWS BACTERIAL/VIRAL

ILLNESS MORTALILY 5-15%, WORSE IN

OLDER CHILDREN & ADULTS

HUS CHARACTERIZED BY

-ACUTE RENAL FAILURE -MICROANGIOPATHIC HA

-FEVER -THROMBOCYTOPENIA (NOT AS SEVERE AS TTP)

HUS 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 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 HEMOLYSIS ELEVATED LIVER ENZYMES LOW PLATLET COUNTS

HELLP SYNDROME 1 IN 1OOO PREGNANCIES SEEN IN PRESENCE OF ECLAMPSIA,

PREECLAMPSIA, AND PLACENTAL ABRUPTION

MAY EXTEND UP TO 6 DAYS POSTPARTUM

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

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

THE END

QUESTIONS????

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

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

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

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