Haematology Watch

Haematology Watch, Vol 1, Issue 1.

CASE RECORDS

A young boy having fever and bleeding multiple sites

Dr. Mehmood-ul-Hasan, Dr. Nazia Khalid

A 15 yrs old boy was brought by parents from Tala Gang on 25.Oct.2008 to the emergency department of Fauji Foundation Hospital with the presenting complaint of:

               -Fever…………….. 1 month

               -Bleeding gums….. 15 days

               -Blood in stool…….. 7 days

He was previously healthy, except for a tendency to heal poorly.

Fever was low grade, intermittent, not associated with shivering or sweating, or specific time of day, and it was not relieved by the medicines he took (i.e. Co-Amoxiclauv).

He also had developed gum bleeding and epistaxis, as well as blood in stool.

Otherwise, the Past Hx, the Family Hx, the Personal Hx, and the Social Hx were unremarkable.

ž  A young boy with average built, co-operative, well oriented to time, place & person:

ž  Pulse: 72/min

ž  Temp.: 98 F

ž  B.P.: 120/80 mmHg

ž  B.R.: 18/min

ž  Pallor: Positive

ž  Jaundice/Clubbing/Cyanosis/Edema/ : Negative

ž  Lymph nodes:  Not palpable

ž  G.I.T: Bleeding left sided gums

ž  C.V.S./C.N.S./Resp. systems: Unremarkable

ž  Temperature of 102F was noted. Cold sponging was advised.

 PROVISIONAL DIAGNOSIS:

ž  Pyrexia of unknown origin

ž  Bleeding disorder

 Following investigations were requested:

ž  Blood CP/ESR                                        Stool for occult blood

ž  Urea/Creatinine                                       Blood for M.P.

ž  Electrolytes                                             Blood for C/S

ž  Stool and Urine R/E

ž  PT, APTT             

ž  CXR

ž  LFT & Hepatitis screening

ž  Tab. ZANTAC (Ranitidine) 150 mg BD

ž  Inj. TITAN (Ceftriaxone Na) 2 g  BD

ž  Inf. D/Saline 1000 cc OD

ž  Inj. BEJECTAL (Vit.B1,B2,B6, Nicotinamide) OD

ž  Tab. PARACETAMOL 1 SOS

ž  Inj. NEUROBION (Vit. B1, B6, B12) OD

ž  Tab. FOLIC ACID 5 mg OD

ž  Inj. VITAMIN-K OD

—  Hb:  (g/dL)                                       15.3                               3.2                               4.4

—  RBC: (3.8-5.8 Х 10¹² /L)                     5.4                                0.9                               1.4

—  Hct: (%)                                            46.5                              9.5                                13

—  MCV: (fL)                                           85                               102                                94

—  RDW:                                                 44                                58                                 50

—  WBC: (/μL)                                    6500                             1800                             1290

—   [ANC]2000-7000                          3700                               576                               230

—   [ALC]1500-3500                           1950                               774                              695

—   [AMC]200-800                                455                               432                              348

—   [AEC] 40-440                                                                       18

—  Platelets:                                 8 000/μL                         2 000/μL                          4 000 /μL

—  Creatinine: ( 60-156 μmol/L)         72                                                                        85

—  P.T.:                                               16/14                             25/13                           20/14

ž  A.P.T.T.                                                                                                                   39/28

ž  Bilirubin: (<17 μmol/L)                                                                                              5

ž  A.L.T.: (U/L)                                    19                                                                       12

—  L.D.H.: (100-250 U/L)                    368

—  Hepatitis B, C serology: Negative

ž  He was transfused 1 unit R.C.C., 2 units Platelets, and 2 units F.F.P.

ž  Pancytopenia due to Acute Leukemia or due to Aplastic anaemia was suspected.

ž  Ultrasound abdomen was requested for status of abdominal viscera.

ž  Simultaneously, Bone marrow examination was advised.

Referring to Peripheral blood smear and Bone marrow examination (Fig.1 and Fig. 2 below), a diagnosis of Acute Promyelocytic leukemia (FAB class AML M3) was made.

ž  The next day his consciousness deteriorated, and multiple bruises at puncture sites developed.

ž  Inj. GENTACIN (Gentamycin), Inj. AUGMENTIN (Co-amoxiclauv), Inj. TRANSAMIN (Tranexamic acid), and O2 INHALATION was started.

Following investigations were requested:

F.D.P.s (D-dimers) for DIC

Serology for Dengue fever (Ig M)

Coagulation profile (INR, APTT, Fibrinogen)

ž  Sohail Khan died on 3^rd day of admission (27^th October) at 8 pm.

Following were his awaited lab. reports:

ž  MP: Not seen

ž  Blood C/S: No growth

ž  FDPs: Pending

ž  Stool for occult blood: Pending

ž  Stool R/E: Pending

ž  Urine R/E: Pending

DISCUSSION

— Acute myeloid leukemias affects all age groups, but are increasingly common with progressing age.

—  The most common genetic abnormality is presence of internal tandem repeats of the FLT-3 gene whose expression is normally tightly regulated in CD34+ cells.

• M0: Minimally differentiated acute myeloblastic leukemia
• M1 : Acute myeloblastic leukemia without maturation
• M2: Acute myeloblastic leukemia with granulocytic maturation
• M3 : Acute promyelocytic leukemia (APL)
• M4 : Acute myelomonocytic leukemia
• M4eo : Myelomonocytic together with bone marrow eosinophilia
• M5 : Acute monoblastic leukemia (M5a)

• M6: Acute erythroid leukemia, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b)
• M7 : Acute megakaryoblastic leukemia

WHO classification

[attempts to be more clinically useful and to produce more meaningful prognostic information than the FAB criteria]

—  AML with characteristic genetic abnormalities:

      [t(8;21)], [inv(16)], or [t(15;17)]

      a high rate of remission

      better prognosis compared to other types of AML.

—  AML with multilineage dysplasia:

      prior MDS or MPD transforming into AML.

      most often in elderly

      worse prognosis.

—  AML and MDS, therapy-related:

      prior chemotherapy and/or radiation and subsequently develop AML or MDS.

      may be characterized by specific chromosomal abnormalities,

      worse prognosis.

—  AML not otherwise categorized:

      subtypes of AML that do not fall into the above categories.

—  Acute leukemias of ambiguous lineage:

     (also known as mixed phenotype or biphenotypic acute leukemia) occur when the leukemic cells cannot be classified as either myeloid or lymphoid cells, or where both types of cells are present.

—  In normal haematopoiesis, the myeloblast is an immature precursor of myeloid white blood cells.

ž  In AML, a single myeloblast accumulates genetic changes which "freeze" the cell in its immature state and prevent differentiation. When such a "differentiation arrest" is combined with oher mutations which disrupt genes controlling proliferation, the result is AML.

ž  Heterogeneity of AML is due to transformation at a number of different steps along the differentiation pathway.

—  The types of chromosomal abnormalities often have prognostic significance. The chromosomal translocations encode abnormal fusion proteins, usually transcription factors whose altered properties may cause the "differentiation arrest." For example, in Acute Promyelocytic leukemia, the t(15;17) translocation produces a PML-RARα fusion protein which binds to the retinoic acid receptor element in the promoters of several myeloid-specific genes and inhibits myeloid differentiation.

—  As the leukemic clone of cells grows, it tends to displace or interfere with the development of normal blood cells in the bone marrow.

—  DIC and AML-M3:

- Pro-coagulant granules released from promyelocytes

- Bleeding from venepuncture sites

- Intracranial bleed

—  Role of All-trans retinoic acid:

- It converts transcription repressors to transcription activators thus resulting in a cellular program for differentiation to mature cells.

-  Although a remission can often be induced with ATRA alone, combining it with chemotherapy (usually daunorubicin and cytarabine) gives better long-term results.

-  The side effects include  retinoic acid syndrome, i.e. breathing problems due to fluid buildup in the lungs, low blood pressure, kidney damage, and severe fluid buildup elsewhere in the body. It can often be treated by stopping the ATRA for a while and giving dexamethasone. During treatment, some patients with APL may also develop blood-clotting problems. They may be given an anticoagulant ("blood thinner") to help prevent or treat this.

References:

—  Essential Haematology by Hoffbrand

—  Wang, Zhen yi, International Bibliographic Information on Dietary Supplements

Fig. 1. Peripheral blood smear of AML-M3

Fig. 2. Bone marrow aspiration slide of AML-M3