This document presents 9 cases involving patients presenting with various hematological abnormalities and disorders. The cases include examples of megaloblastic anemia, Fanconi anemia, aplastic anemia, paroxysmal nocturnal hemoglobinuria, acute lymphoblastic leukemia, acute myeloid leukemia with myelomonocytic features, myelodysplastic syndrome, disseminated tuberculosis, hypersplenism and hemophagocytic syndrome. For each case, the patient history, physical findings and diagnostic workup are provided, along with the diagnoses and relevant background information.

1. CASE 1

2. HISTORY
•A 30yrs old male,presented to OPD
with malaise, tiredness and
weakness.
•He is a known alcoholic.

3. PHYSICAL FINDINGS

4. INVESTIGATIONS
• PERIPHERAL BLOOD SMEAR- Anisopoikilocytosis
- Macro-ovalocytes
- Hypersegmented Neutrophil
• RBC INDICES- MCV- 110
- RETICULOCYTE COUNT- low

6. DIAGNOSIS??

7. MEGALOBLASTIC ANEMIAS
DEFINITION-
• Impaired DNA synthesis due to
deficiency of vitamin B12
and folic acid.

8. Biochemical Assays-
• Serum B12 & Folate levels – Automated chemiluminescence
• Serum LDH levels
• Serum Methylmalonic acid & Homocysteine levels – HPLC
• Intrinsic factor antibody test
• Serum gastrin or gastric juice Ph
Upper GI endoscopy and biopsy – Villous atrophy

9. •Increase in Homocysteine and Methy
malonic acid – Vit B 12 Deficiency
•Only increase in Homocysteine : Folate
deficiency

10. ATROPHIC GLOSSITIS KNUCKLE
HYPERPIGMENTATION

12. “BONE MARROW EXAMINATION IS NOT
REQUIRED FOR THE DIAGNOSIS OF
MEGALOBLASTIC ANEMIA”

13. CASE 2

14. HISTORY
• A 10yrs old girl presents with pallor and
weakness.
• Congenital anomalies seen
• Family history of cancer.

15. PHYSICAL FINDINGS
EPICANTH
AL FOLDS
ABSENT
THUMB
SHORT
STATUR
E
MICROCEPH
ALY
HYPERPIGMENTA
TION
HYPOGONAD
ISM
ABSENT
RADIUS

16. DIAGNOSIS??

17. FANCONI ANEMIA
• Inherited syndrome
• Autosomal recessive
• Includes- Pancytopenia
- Congenital anomalies
- Cancer susceptibility

18. FURTHER WORK-UP
• Demonstration of increased chromosomal
breakage in the presence of DNA cross-
linking agents such as MITOMYCIN C or
DIEPOXYBUTANE

20. “No other constitutional
pancytopenia is associated
with an abnormal
chromosomal breakage study”

21. CASE 3

22. HISTORY
•A 55yrs old male on chemotherapy
presents with pallor and dyspnea.
•Also complains of petechiae and
frequent minor infections.

23. INVESTIGATIONS
• PERIPHERAL BLOOD SMEAR-
Pancytopenia
• BONE MARROW ASPIRATION- Dry tap

25. DIAGNOSIS??

26. FURTHER WORK-UP
• BONE MARROW BIOPSY-
Hypocellular marrow
• No Splenomegaly

27. HYPOCELLULAR BONE MARROW BIOPSY

29. CRITERIA FOR SEVERE APLASTIC ANEMIA
At least 2 of the following peripheral blood findings:
• Reticulocytes <1%, corrected for hematocrit
• Absolute neutrophil count <500/μL (0.5 × 109/L)
• Platelets <20,000/μL (20 × 109/L)
• AND
• Bone marrow biopsy with <25% normal cellularity
• OR
• Bone marrow biopsy with <50% normal cellularity in which less
• than 30% of the cells are hematopoietic

30. CAUSES OF APLASTIC ANEMIA
ACQUIRED(80%)
• Idiopathic
• Drug induced
• Viral (hepatitis, EBV)
• Ionising radiation
• Toxins (pesticides,
benzene, arsenic)
• Pregnancy
• Leukaemia
INHERITED(20%)
• Fanconi Anaemia
• Dyskeratosis congenita
• Shwachman-Diamond
syndrome
• Diamond-Blackfan anemia

31. DRUGS CAUSING APLASTIC ANEMIA
• Anti cancer drugs :Alkylating agents
Antimetabolities
Antimitotics
• Antibiotics : Streptomycin
Tetracycline
Methicillin
Chloramphenicol
• Anti inflammatory drugs : Indomethacin
Ibuprofen
Aspirin

32. • Anti thyroid : Methimazole
Methylthiouracil
Propylthiouracil
• Anti hypertensive : Methyldopa
• Anticonvulsants : Hydantoins
Carbamazepine
• Antihistaminics : Cemitidine
Chlorpheniramine

33. “Most common cause Of
Aplastic Anemia is
IDIOPATHIC”

34. CASE 4

35. HISTORY
• A 20yr old male presents with sudden onset
malaise and fatigue with recurrent
abdominal pain.
• He also complains of dark color urine on
waking up.

36. INVESTIGATIONS
• PERIPHERAL BLOOD EXAMINATION-
Hemolytic picture seen
• BONE MARROW EXAMINATION-
Hypoplastic

37. DIAGNOSIS??

39. FURTHER WORK UP
• HAM’S TEST

40. FLOW CYTOMETRY

41. PAROXYSMAL NOCTURNAL
HAEMOGLUBINURIA
• PNH arises as a result of nonmalignant clonal
expansion of one or more hematopoietic stem
cells that have acquired somatic mutation of the
X-chromosome gene PIGA
(phosphatidylinositol glycan class A)

42. “ Best Diagnostc
test of Paroxysmal
Nocturnal
Haemoglobinuria
is by FLOW
CYTOMETRY ”

43. CASE 5

44. HISTORY
• A 8yr old child comes with sudden onset fever
and fatigue.
• Also gives history of recurrent pneumonia.
• On examination- generalised lymphadenopathy
present.

45. INVESTIGATIONS

46. DIAGNOSIS??

47. FURTHER WORK-UP
• CYTOGENETIC STUDY- t(12;21) present.

48. ACUTE LYMPHOBLASTIC
LEUKEMIA

49. ACUTE
LYMPHO-
-BLASTIC
LEUKEMIA

50. CASE 6

51. HISTORY
• A 40 yrs old male complains of fever and
malaise.
• On examination had gum hypertrophy and
splenomegaly.

52. INVESTIGATIONS
• PERIPHERAL BLOOD EXAMINATION-

53. DIAGNOSIS
??

54. ACUTE MYELOID LEUKEMIA- M5

55. FURTHER WORK-UP
• BONE MARROW EXAMINATION-

56. CASE 7

57. HISTORY
• A 70 yrs old male patient complains of
fever and weakness.
• He has history of recurrent infections.
• History of unprovoked bleeding from skin
and gums.

58. INVESTIGATIONS
• PERIPHERAL BLOOD EXAMINATION-
Pancytopenia
- Nucleated RBC’s
- Neutrophil with two lobes

59. DIAGNOSIS??

60. FURTHER WORK-UP
• BONE MARROW EXAMINATION- Ring sideroblasts seen
- Megakaryocytes with multiple nuclei.

61. MYELODYSPLASTIC SYNDROMES
• The myelodysplastic syndromes (MDS) are clonal
hematopoietic stem cell disorders characterized by
cytopenias with cellular marrow and a risk for
leukemic transformation.
• Features of dysplasia of hematopoietic cell lines with
impairment of proliferation and differentiation of these
cells.
• Hallmark – Ineffective hematopoiesis

62. CASE 8

63. HISTORY
• A 40 yr old male presents with fever and cough.
• He also complains of fatigue and weakness.
• On examination shows enlarged cervical lymph
nodes.

64. INVESTIGATIONS
• CHEST X-RAY- Shows pleural effusion.
• PERIPHERAL BLOOD SMEAR-
Pancytopenia.

66. DIAGNOSIS??

67. FURTHER WORKUP
• BONE MARROW EXAMINATION-
Granuloma
• ZN STAIN- Shows acid fast bacilli.
• HIV POSITIVE

68. DISSEMINATED TUBERCULOSIS

69. Granuloma in a trephine biopsy section of
bone marrow from a
patient with AIDS and disseminated
atypical mycobacterial infection. H&E
Bone marrow granuloma from a patient with
AIDS and disseminated Mycobacterium avium
intracellulare infection. The macrophages
contain many acid-fast bacillli. Ziehl–Neelsen
stain

70. CASE 9

71. HISTORY
• Mr. A 55yrs old male patient, a railway
worker, consulted his doctor for tiredness,
malaise and anorexia.
• He was found to be mildly jaundiced with
an enlarged irregular hepatomegaly and
considerable ascites.

72. INVESTIGATIONS
• PERIPHERAL BLOOD SMEAR- Anisopoikilocytosis
- Macrocytosis
- Target cells
- Stomatocytes

73. DIAGNOSIS??

74. FURTHER WORKUP
• SONOGRAPHY- Enlarged spleen
• BONE MARROW EXAMINATION-
Normocellular marrow with hematopoeisis
• HEPATITIS VIRUS STUDIES- Negative for A,
B and C.

75. HYPERSPLENISM
• Splenic hyperactivity with increased blood cell destruction.
Diagnostic criteria
1. Splenomegaly
2. Pancytopenia
3. Normal or hypercellular bone marrow
4. Reversibility by splenectomy

76. HAEMOPHAGOCYTIC SYNDROME
• Also called Hemophagocytic lymphohistiocytosis
Clinical features
• Fever
• Hepatosplenomegaly
• Jaundice
• Lymphadenopathy
• Rash

78. LABORATORY FINDINGS
• Histiocytosis
• Hemophagocytosis
• Pancytopenia
• Eleveted serum ferritin
• Elevated liver enzymes

79. DYSKERATOSIS CONGENITA
• RARE inherited disorder.
• X-linked Recessive, autosomal dominant,
autosomal recessive.
• Pancytopenia + dematological
manifestation.
• Nail dystrophy and leukoplakia.

80. Mutations in DKC1 at band Xq28
Dermatological manifestations

81. INFECTIONS
• HIV
• Infectious mononucleosis
• Hepatitis B
• Hepatitis C
• Measles
• Hepatitis A
• Parainfluenza
• Influenza