Acute Liver Failure + Drug Induced Liver Injury ec OAT +

Drug reaction with eosinophilia and systemic symptoms

+ TB mammae Dextra + Hipoglikemia ec Iiver
involvement + Hiponatremia ec low intake

Selasa, 7 Desember 2021

Jerry Tjoanatan
Tiene Rostini, dr. Sp.PK(K)

T I N J A U A N K A S U S K I M I A
Uraian Kasus
Identitas Pasien

• Nama : Ny D.D.R • Asal Ruangan/Bagian: MIC/ Fresia 2 / IPD

• Jenis kelamin : Perempuan • Masuk RS : 27 Februari 2019
• Umur : 09/12/1992 • Keluar RS : 03 Maret 2019
(26 tahun) (meninggal)
• Alamat : Kab. Bandung • Lama perawatan: 5 hari
• Rekam Medik : 0001747913 • Status : JKN PBI

2
 Anamnesis (autoanamnesis)
Keluhan Utama :
• Mata kuning sejak 4 hari
• Panas badan sejak 7 hari disertai ruam kemerahan

(2 bulan SMRS): (4 hari SMRS) :

• TB mammae dextra (3 bln SMRS) • Mata kuning; BAK seperti teh; mual muntah
• Terapi OAT sejak 1 bln SMRS(+) • Kulit mengelupas

(7 hari SMRS) :
• Demam
• Pusing
• Ruam kemerahan

3
 Pemeriksaan Fisik
● Keadaan Umum : Sakit sedang Kepala :
● Kesadaran : CM Conjungtiva anemis (+/+)
● BB/TB : 40kg/150cm (IMT : 17,8) Sklera ikterik (+/+)
● Tanda Vital: frenulum lingueae ikterik (+)
• TD : 120/70 mmHg Leher dan Thoraks : dbN
• Nadi : 100x/menit, irama Abdomen : NT area epigastrium (+)
reguler, isi cukup hepatomegali (+)
• HR : 100x/menit, irama reguler Ekstremitas : maculopapular eritema (+)
• Suhu : 38,0 oC
Status dermatologis : distribusi generalisata
• Resp : 20 x/menit Perut, leher, lengan bilateral, tungkai bilateral  lesi multiple,
sebagian konfluens, bentuk ireguler : uk. 0,2x0,2 cm, Perut :
tampak kering, lesi rata dg permukaan  purpura, makula
eritema + skuama diaskopi(+) pada bercak merah di lengan
4
 Pemeriksaan Penunjang
Pemeriksaan Hasil Rujukan Satuan Interpretasi
Hematologi         IGD 27/2/2019 (hari ke-1)
Hemoglobin 9,4 P: 12,3-15,3 g/dl  Rule of 3
Hematokrit 27,2 P: 36-45 %  Hb x 3 = Ht ± 2
Eritrosit 3,96 P: 4,2-5,5 juta/uL  9,4 x 3 = 28,2 (√)
Leukosit 23.530 4.500-11.000 /mm 3 ↑ Eri x 3,3 = Hb ± 1,5
Trombosit 534.000 150.000-450.000 /mm3 ↑ 3,96x3,3= 13,07 (X)
MCV 68,7 80-96 fl  Eri x 9 = Ht ± 3
MCH 23,7 27,5-33,2 pg  3,96x9 = 35,64 (X)
MCHC 34,6 33,4-35,5 % N
Hitung Jenis Leukosit         Morfologi Darah Tepi
Basofil 0 0-1 % N Eritrosit : NAP (target cell,
Eosinofil 14 0-4 % ↑
N
cigar shape, burr cell) ;
Neutrofil Batang 0 3-5 %
Neutrofil Segmen 29 45-73 %  normoblast 1/100 leukosit
Limfosit 39 18-44 % ↑ Leukosit : Jumlah ↑, limfosit
Monosit 4 3-8 % N atipik (+), ditemukan tersangka
Tersangka Blast 14 % blast dg sitoplasma sedikit
  Total Basofil 0,00 0,01-0,09 10 /uL
3 N
↑
s/d sedang, kromatin inti halus,
Total Eosinofil 3,29 0,01-0,40 103/uL
Total Neutrofil 6,82 2,10-8,89 103/uL N anak inti tidak jelas s/d 2
Total Limfosit 9,17 1,26-3,35 103/uL ↑  Trombosit : Jumlah ↑, tersebar
Total Monosit 1,14 0,29-0,95 103/uL Kesan : Reaksi leukemoid dd/
tersangka leukemia 5
Pemeriksaan Hasil Rujukan Satuan Interpretasi
Kimia           Pemeriksaan Penunjang
Glukosa Sewaktu 63 <140 mg/dL N
SGOT(AST) 433 15-37 U/L ↑ IGD 30/12/2019 (hari ke-1)
SGPT(ALT) 1156 14-59 U/L ↑
Bilirubin Total 13,266 0,100-1,000 mg/dL ↑
Bilirubin Direk 9,884 0,100-0,300 mg/dL ↑ Radiologi : (foto thoraks)
Bilirubin Indirek 3,382 0,200-0,800 mg/dL ↑ Tidak tampak kardiomegali ;
Ureum 16,0 15-39 mg/dL N Tidak tampak proses spesifik;
Kreatinin 0,75 0,80-1,30 mg/dL N Elevasi diafragma kiri
Natrium 129 135-145 mEq/L 
Urinalisis Rutin EKG :
Makroskopis Sinus takikardi, rate 109 bpm
Warna Kuning tua Kuning AbN
Kejernihan Agak keruh Jernih AbN
Kimia Urine
Keton 2+ Negatif ↑
Bilirubin 3+ Negatif ↑
Leukosit esterase 3+ Negatif ↑
Eritrosit 3+ Negatif ↑
Mikroskopis
Eritrosit 10-19 0-3 /LPB ↑
Leukosit 5-9 0-5 /LPB ↑
Epitel 5-9 0-1 /LPK ↑

6
 DIAGNOSIS KERJA:
Drug Induced Liver Injury ec OAT + Possible Drug Reaction with Eosinophilia
and Systemic Symptomps (DRESS) + TB mammae Dextra on OAT kategori I
bulan ke 2 + Hipoglikemia ec liver involvement + Hiponatremia ec low intake

Tatalaksana
• IVFD D10% 1500 cc / 24 jam  Diet 1250 kkal / 24 jam
• Bedrest  Cek GDS, ALP, GGT, PT/INR,
• Vas Albumin 2x / hari Albumin, HBsAg, anti HCV
• Cetirizine 1x10 mg po  USG Abdomen
• Metilpredinisolone 40 mg-0-0 po  Cek SGOT dan SGPT / 3 hari
• N-acetylcystein 3x200 mg po  Rawat ruang biasa
• Stop OAT

Prognosis: quo ad vitam et functionam dubia ad bonam

7
 Follow Up (Fresia)
Tgl 28/2/19 1/3/19 2/3/19 3/3/19
Hari Ke Hari ke -2 Hari ke -3 Hari ke - 4 Hari ke – 5
Subject: Mata kuning (+), Mata kuning (+), Mata kuning (+), Mata kuning (+),
NTE(+), NTE(+), demam(+), gatal mual/muntah(-);
mual/muntah(-) mual/muntah(-); seluruh tubuh; demam(+), gatal
demam(+) gelisah seluruh tubuh;
gelisah
Objective TD: 110/70 mmHg TD: 100/70 mmHg TD: 120/80 mmHg TD: 110/70 mmHg
RR: 20 x/menit RR: 20 x/menit RR: 16 x/menit RR: 24 x/menit
HR: 80 x/menit HR: 88 x/menit HR: 84 x/menit HR: 100x/menit
S: 37,0 °C S: 36,7 °C S: 36,8 °C S: 36,9 °C
Assesment stqa stqa stqa ↓ kesadaran ec
metabolik, lain stqa
Planning Sesuai catatan Inj OMZ 1x40 mg iv Sesuai catatan Konsul MIC
pengobatan CaCO3 3x50 mg po pengobatan IVFD NaCL 0,9%
Lain2 sesuai catatan O2 3LPM/nc
pengobatan NGT, lain2 stqa

8
Tgl 28/2/19 1/3/19 2/3/19 3/3/19
Hari Ke Hari ke -2 Hari ke -3 Hari ke - 4 Hari ke – 5
Lab Kimia Kimia Kimia Hematologi
GGT : 233 U/L GDP : 44 mg/dL GDP : 120 mg/dL Hb : 8,5 g/dL
ALP : 134 U/L GD2PP : 134 mg/dL GD2PP : 117 mg/dL Ht : 25,5%
TP : 5,3 g/dL SGOT : 438 U/L Eri : 3,66 x106/µL
Alb : 1,66 g/dL SGPT : 829 U/L L : 14.210 /µL
Glob: 3,6 g/dL T : 594.000 /µL
Ratio A/G : 0,46 MCV : 69, 7 fL
MCH : 23,2 pg
MCHC 33,3 %
Imunoserologi Kimia
HBsAg kromato : Nore GDP : 238 mg/dL
Anti HCV Rapid : Nore Bil. Tot : 15,570 mg/dL
Ureum : 7 mg/dL
Kreatinin : 1,06 mg/dL
Hemostasis Hemostasis
PT : 55,30 detik PT : > 120 detik
INR : 5,43 INR : > 9
APTT : 91,20 detik APTT : 146,4 detik

AGD : asidosis metabolik terkompensasi

sebagian dengan hipoksemia dan kadar
O2 rendah 9
 Follow Up (MIC)
Tgl 3/3/19
Hari Ke Hari ke – 5 (19.15) (19.38)
Subject: Penurunan kesadaran Henti napas
sesak napas, demam

Objective Kes : coma RR: 0 x/menit

KU : tsb PR: 0 x/menit
TD: 110/70 mmHg
RR: 30 x/menit
HR: 124 x/menit S:
38,8 °C
SpO2 88% 15 LPM/nrm
Assesment stqa Cardiac arrest

Lab RJP
Pasien meninggal
pukul 19.50

10
 Analisis Kasus

Keluhan Utama : mata kuning, demam dan lesi kulit

• TB mamae
• Demam
Dextra on OAT DRESS
• Lesi kulit : EM
sejak 2 bulan
• Eosinofilia
SMRS

• Jaundice
• Ensefalopati ALF
• Hepatomegali
DILI • NT UQA

11
 Jaundice Ikterik Hepatitis
• Hiperbilirubinemia > 3 mg/dL • < 6 bulan = akut
• Direk / Indirek / Mixed • inflamasi parenkim  hepatosit
• Pre/ Hepatik / Post • Paling sering : infeksi ; lainnya :
• Acute  Hepatitis (infeksi/ non non infeksi
infeksi)/ Toxic ec OAT • OAT (RHZ) /obat2an  DILI
• ALT >> 5x BAN; ALP >> 2x BAN
Demam S : 38 °C TB mammae
• Suhu >> di atas set point • TB extra paru
• Pirogen • Jarang , insiden s/d 4%
• Paling sering : infeksi ; • Benjolan , nyeri (-) awalnya, unilat
lainnya : non infeksi
• Bila berlanjut  abses, ulcer,
• Demam 7 hari = akut mastitis difus
• OAT lini 1 (RHZE) 12
 Eritema Multiformis
• Rx hipersensitivitas mukokutaneus akut
• Kerusakan sel epitel : respons imun seluler
• influks makrofag + limfosit T CD8 berbagai sitokin inflamasi  kematian sel
• Infeksi / rx hipersensitivitas obat
• penisilin, sefalosporin, makrolida, sulfonamid, agen anti tuberkulosis, antipiretik
• Onset lambat  Rx Hipersensitivitas obat  DRESS
• defisiensi enzim detoksifikasi (genetic)  akumulasi metabolit obat  kematian sel /
respons imun 2nd
• Sel T  IL5  eosinophilia
• Kriteria : RegiSCAR (5 of 6)/ Japanese Group‘s criteria (7)

13
 Penurunan kesadaran Ensefalopati Hepatik
• 3 Mekanisme : • perubahan kepribadian, gangguan
• lesi otak struktural, intelektual, dan penurunan tingkat
kesadaran
• disfungsi saraf difus sekunder
akibat gangguan sistemik, • + disfungsi hepar  ALF
• psikiatri (jarang) • Edema otak
• Disfungsi saraf difus – sistemik : • ↑ permeabilitas BBB,
metabolic • gangguan osmoregulasi, dan
• Ensefalopati dan hipoglikemia • ↑ aliran darah otak West Haven
Criteria
ALF Gejala dan tanda
• Kerusakan fungsi hepar yang • Ensefalopati; • Δ uk. hepar:
cepat • Edema serebri; • Hematemesis-
• Jaundice; melena;
• Koagulopati (INR > 1,5)
• Ascites; NT • Hipotensi +
• Gangguan kesadaran takikardia
RUQA
• Akut Fulminan  < 8 minggu
14
 ALF Komplikasi
• Koagulopati (INR ≥ 1,5) • Edema serebri;
• Gangguan kesadaran • Infeksi;
• ↑ bilirubin dan ALT, • Koagulopati + perdarahan
• Trombositopenia, anemia, • AKI; Sindrom Hepatorenal
• hipoglikemia, • Kardio-pulmonal
• ↑ amonia dan • Ggn asam-basa + metabolism
• gambaran AKI (↑ kreatinin serum), dan • Hipoglikemia
• gangguan elektrolit) • Ggn elektrolit

Hipoglikemia
• Buffering organ  KH
• Mekanisme
• Ggn gluconeogenesis – hepatosit <<<
• Uptake insulin <<< krn resistensi insulin 15
 Anemia defisiensi Fe

Morfologi Anemia hipokrom mikrositer

TB mammae  anemia disebabkan oleh IMT <, hipoalbumin , hiponatremia 

defisiensi nutrisi, sindrom malabsorpsi, defisiensi nutrisi
kegagalan pemanfaatan zat besi, dan Cadangan Fe <<  produksi
supresi sumsum tulang megakariosit  Trombositosis

16
 Hiperbilirubinemia
• DILI  ALF Hipoalbuminemia
• kerusakan hepatosit akut
Hipoglikemia
↑ALT, AST, ALP, GGT • penurunan cadangan glikogen
• ALT >> spesifik • resistansi insulin dan penurunan
• sintesis ALP ↑ glukoneogenesis
• GGT + abN fx hepar lain 
kerusakan hepatosit
15,570 mg/dL
13,266 mg/dL

1155 U/L

829 U/L

1,66 g/dL
433 U/L 438 U/L
233 U/L

134 U/L
Bilirubin total
Albumin
17
 Leukositosis
• Akut / Kronis Rx Leukemoid
• Respons inflamasi • Leukosit >50.000 /uL
• Limfositosis • peningkatan neutrofil matur dan
• infeksi virus, "shift to the left"  IG
• reaksi hipersensitivitas,
• penyebab reaktif di luar sumsum
• leukemia, dan limfoma
tulang
• disfungsi dari neutrofil yang terjadi
pada ALF • infeksi berat, intoksikasi, keganasan,
perdarahan hebat, dan hemolisis akut
• Eosinofilia  DRESS serta dapat mengikuti paparan obat.
• Pada ALF
• adult T-cell leukemia (ATL)

18
 Ketonuria Koagulopati
 peningkatan benda keton   PT dan APTT memanjang, INR
masa kelaparan meningkat
 Dapat menyebabkan  Hepar : tempat sintesis semua faktor
ketoasidosis koagulasi (fibrinogen dan faktor II, V,
 Produksi asam >>>  VII, VIII, IX, X, XI dan XII) dan
Penurunan HCO3-  inhibitor faktor koagulasi kecuali
asidosis metabolik faktor von Willebrand (vWf)
 Hepatosit rusak pada ALF  sintesa
<<<, defisiensi vit K
Urinalisis
• DRESS  nefritis
• Leukosit esterase + Infeksi /
inflamasi
• Hematuria + dan Blood 3+
• Bilirubinuria  B.Direk
19
 Simpulan

Perempuan (26 tahun) datang dengan keluhan mata kuning sejak 4 hari + BAK seperti teh,
panas badan sejak 7 hari SMRS dan lesi kulit kemerahan dan mengelupas Pasien sedang
dalam terapi OAT ec TB mammae dan didapatkan penurunan kesadaran di hari ke 5

Pemeriksaan fisik → IMT kurang, takikardia, suhu febris, conjungtiva anemis (+), sklera
ikterik (+) facial pallor (+), frenulum lingueae ikterik (+), NT epigastrium (+), Hepatomegali(+)
Lesi kulit maculopapular eritema

Pemeriksaan laboratorium
Anemia sedang hipokrom mikrositer, leukositosis dg limfositosis dan eosinophilia, reaksi
leukemoid, hiperbilirubinemia, AST dan ALT ↑ >10x BAN, ALP dan GGT ↑, hipoglikemia GDP,
ureum / kreatinin ↑; hiponatremia (+), asidosis metabolik terkompensasi sebagian dengan
hipoksemia dan saturasi oksigen rendah; bilirubinuria, hematuria, leukosit esterase (+)

20
 Diagnosis Akhir
Acute Liver Failure + Drug Induced Liver Injury ec OAT + Drug
reaction with eosinophilia and systemic symptoms +
TB mammae Dextra on OAT kategori I bulan ke 2 + Hipoglikemia
ec liver involvement + Hiponatremia ec low intake
Permasalahan Saran

1. Follow up GD tidak terdokumentasi dengan 1. Pemeriksaan laktat bersamaan AGD

baik  hipoglikemia  memperburuk
kondisi
2. Laktat tidak diperiksa  mengetahui
kerusakan hati dan severitas
3. Elektrolit tidak diperiksa  ggn
sebelumnya
4. CT scan tidak sempat dilakukan 
menyingkirkan kemungkinan stroke
iskemik
2. Pemeriksaan ammonia baik darah atau
urine  menegakkan diagnosis
ensefalopati hepatic
3. Pemeriksaan elektrolit Natrium serial 
dapat terjadi berulang  karena pasien
penurunan kesadaran.
4. Pemeriksaan EKG serial  miokarditis
5. Pemeriksaan pewarnaan dan kultur
sputum  pneumonia
21
Skema Analisis Kasus

22
Terima Kasih
Hepatic Encephalopathy

Liver failure  utilization of ammonia in

hepatic urea cycle ↓ (the major
ammonia detoxification pathway) +
portosystemic shunting  accumulation
of ammonia systemic  crosses BBB
Cerebral ammonia detoxification via
glutamine synthetase  astrocytes
(main excitatory and inhibitory
neurotransmitters: GABA) 
• osmotic effect  swelling + cytotoxic
edema
• induce changes in cerebral
neurotransmission : glutamate >>>-
induced N-Methyl-D-aspartic acid
(NMDA)-receptor activation, 
neuronal death.
• DRESS/DiHS,  new biomarkers : cytokines + chemokins released from activated T cells.
• IL-6 and interferon gamma-produced protein 10 (IP-10)
• IL-16
• Indicators of disease progression and activity :
serum thymus and activation-regulated chemokine (TARC)
~ drug-induced hypersensitivity syndrome (DIHS)

• incidence : 10 / per million person-years

• symptomps : fever, rash,lymphadenopathy, hepatitis, and
leukocytosis with eosinophilia.
• earliest phase : periorbital and facial edema + erythema with
pinhead-sized pustules.
• cervical, axillary, and inguinal lymphadenopathy

Pathophysiology :
• activated T cells : CD4+ dominant T-cell infiltration (type IVb)
• Th1 and other components : B cells, IgE, IgG4, mast cells,
eosinophils  marked secretion of IL-4, IL-5 and IL-13
• B : directly binding non-
covalently to either T-cell
receptor (TCR) or HLA (without
antigen processing)stimulate
T cells
• A : endogenous proteins
covalently bind drug or its
metabolites  forming a
neoantigen  triggers T-cell
response
• C : causal drug  HLA peptide
binding groove --> altering
binding cleft and specificity of
self-peptides able to bind to the
HLA molecule
 Drug-induced
exanthemata /
DRESS

• Idiosyncratic
• Classically, APC present
haptens(composed of the drug or its
metabolite bound to a protein or
peptide) to naive T cells → antigen-
specific T cells proliferate, infiltrate
the skin + release cytokines,
chemokines, other proinflammatory
mediators → drug-related rash
• Alternatively, the p-i (pharmacologic
interaction of drugs with immune
receptors) concept → small-
molecule drugs or their metabolites
→ activate T cells directly by binding
to T-cell receptors
● Eruption is most commonly urticaria-
like plaques or an exanthem
● Fever, edema (particularly facial and
acral), lymphadenopathy, leukocyte
abnormalities (leucocytosis,
eosinophilia and/or atypical
lymphocytosis) hepatitis and non-
erosive mucositis
● Less frequent : Nephritis,
pancreatitis, pneumonitis and
myocarditis
● Immunopathogenesis :
○ variations in class I and class II HLA
genes suggesting that CD4+ and/or CD8+
T-cell immune responses
Drug-induced Liver Injury
● DILI  leading cause of ALF in the US
○ estimates of global incidence of DILI : 13.9 per 100,000
patients per year
○ occurs within 2 months after administration
○ highest incidence occurs in 1st 2 weeks.
● Classified as intrinsic (or direct) vs. idiosyncratic.
● Intrinsic DILI
○ is typically dose-related and
○ occurs in a large proportion of individuals (predictable)
○ onset is within a short time span (hours to days).
● Idiosyncratic DILI
○ is usually not dose-related,
○ occurs in only a small proportion of individuals (unpredictable)
○ exhibits a variable latency to onset of days to weeks
● Approximately 10% of patients with
drug-induced jaundice  die from
ALF or require a liver transplantation.
● And approximately 90%  survive
● Hepatocellular type of DILI :
○ a poor outcomes  higher liver-related
mortality
HAART, highly active antiretroviral therapy.
**Mild ALT elevations without jaundice
§Both intrinsic and idiosyncratic.
 The laboratory profile of DI

• Classify the type of IDILI, an R ratio alanine aminotransferase (ALT) and alkaline
phosphatase (ALP) levelsl:
• ≤ 2 indicates cholestatic liver injury,
• ≥ 5 indicates hepatocellular liver injury, and
• intermediate values indicate a mixed phenotype.
• High serum aminotransferase levels + jaundiced DILI  greater likelihood of early death/
• transplant  Hy's law = serum ALT > 5X ULN with elevated total bilirubin

• Particular HLA class II molecules  pattern of liver injury

• 2 underlying mechanisms :
• related to genetic polymorphism (single nucleotide polymorphisms) of cytochrome P-450
(CYP),  lead to formation of toxic derivatives of drug  bind covalently to hepatic
constituents.
• protective mechanism to inactivation of reactive metabolites may fail.
 Biomarkers of DILI pathogenesis and outcomes

The serum biomarkers most commonly used to detect and manage most forms of
acute and chronic liver injury are
• serum ALT, alkaline phosphatase and total bilirubin levels

The new serum markers

1. Liver injury : (sorbitol dehydrogenase (SDH), glutathione s-transferase, GSTα)
2. Mitochondrial dysfunction from disrupted hepatocytes (glutamate
dehydrogenase or GLDH)
 EPTB (EXTRA PULMONAL TUBERCULOSIS)
• The immunochemistry-based MPT64 antigen detection test (MPT64 test)
•  in low-resource settings = higher sensitivity than microscopy and culture.
• biopsies, fine-needle aspirates (FNAs) and fluid samples
• Sensitivity of microscopy for acid fast bacilli (AFB) and culture, is low in
paucibacillary disease
• Culture : requires advanced laboratory facilities, and results delayed up to 8 
weeks  gold standard
• Rapid molecular tests for detection of TB
• T-cell interferon-γ release assays (IGRAs) – blood or body fluid
• lymphocytes in response to Mycobacterium tuberculosis (MTB)-specific antigens,
• early secretory antigenic target 6 (ESAT-6) and
• culture filtrate protein-10 (CFP-10)
 EPTB (EXTRA PULMONAL TUBERCULOSIS)

IGRAs on blood sensitivity and specificity for the diagnosis of EPTB :

• 72% and 82%, - QuantiFERON-TB Gold
• TB lymphadenitis was 81.8% and 80.0%,
• but 38.5% and 50.0% in patients with TB pleurisy
• 90% and 68% - T-SPOT.TB
• more sensitive  chronic forms of EPTB : lymph node or osteoarticular TB
(89% and 100%)
• acute forms of EPTB :TB meningitis (74%)
• Diagnostic value of blood IGRA is more limited in TB
meningitis or TB pleurisy  relatively low sensitivities
When hepcidin level is abnormally low, on
the contrary, iron overload occurs due to
increased iron efflux from storage and gut
iron absorption.
Iron Deficiency
Anemia
 Anemia Hemolytic in Liver disease
• Liver disease  structural and metabolic abnormalities of the erythrocyte
membrane  cell shape changes and hemolytic anemia
 Increase in unesterified serum cholesterol owing to lecithin cholesterol
acyl transferase (LCAT) deficiency in liver failure  expansion of the
lipid bilayer and macrocytosis without megaloblastic changes in
precursors.
 Substitutions of phosphatidyl choline (PC) moieties in the erythrocyte
lipid bilayer  echinocytes (disaturated PC) or to stomatocytes
(diunsaturated PC).
 high density lipoprotein (HDL) abnormalities  echinocytes.

• vitamin E deficiency  lipid peroxidation and pyruvate kinase

instability  adenosine triphosphate (ATP) reduction  hemolysis

• most severe hemolysis  acanthocytes (spur cells) and a marked

imbalance in cholesterol-phospholipid ratio
Terima Kasih