1. Tuberculosis can cause a wide range of hematological changes including anemia, leukocyte abnormalities, thrombocytopenia, pancytopenia, and coagulation disorders. 2. Common findings include normocytic anemia, leukocytosis or leukopenia, lymphocytopenia, thrombocytosis or thrombocytopenia, and elevated ESR. 3. Bone marrow changes include hypercellularity, myeloid hyperplasia, erythroid hyperplasia, megaloblastic changes, and sometimes granulomas. 4. Some hematological abnormalities are reversible with antituberculosis treatment, while anti-tuberculosis drugs can also cause hematological side effects like anemia, leuk

1. Dr.Prabhakar K

2.  Introduction
 Hematological changes due to disease
Blood & Bone marrow changes
 Hematological changes due to drug ( ATT)

3. Tuberculosis is a chronic bacterial infection caused by
Mycobacterium tuberculosis.
This ancient infection has plagued humans through ages.
 Its elimination has remained extremely
difficult as long as poverty, over population, HIV
infection exists in large portions of earth .
 It is an index of social organization and standard of living
in the community

4. Tuberculosis can affect any organ.
Lung is usual site involved.
The extra pulmonary sites involved are lymph nodes,
pleura, genitourinary tract, bones, joints, meningeal,
peritoneum.
 Today as a result of hematogenous dissemination in
HIV infection, extra pulmonary is seen more
commonly than in the past.

5. Hematopoietic system is another organ seriously
affected by tuberculosis.
 It exerts a dazzling variety of hematological effects
involving both cell lines and plasma components.

6.  The hematological changes sometimes act as
useful factors providing a clue to diagnosis,
assessing the prognosis, indicating the
complication of underlying infection as well as
therapy and response to therapy .

7. Focal and disseminated tuberculosis.
Reversible with ATT.
Infectious process itself or consequence of ATT

8. Hematological changes in TB
 Anemia (normochromic normocytic/microcytic)
 Leucocyte changes
Leucopenia or leucocytosis
Lymphocytopenia
Neutropenia or neutrophilia
Monocytopenia or monocytosis
Basophilia
Isolated eosinophilia

9.  Thrombocytopenia or thrombocytosis
 Pancytopenia
 Deep vein thrombosis
 Disseminated intravascular coagulation
 Raised ESR

10. Anaemia
TB (Chronic Inflammatory response)
Increased secretion of Cytokine TNF α
Decrease response to Erythropoietin
Decrease utility of bone marrow iron stores

11.  Anaemia in pulmonary tuberculosis may also occur as a
consequence of chronic inflammation , and without
apparent loss of blood or bone marrow suppression
(Baynes et al. 1986a)
 Blunted response of erythropoietin due to release of
tumour necrosis factor a or other cytokines have
been observed (Ebrahim et al1995)
 Tuberculosis is a chronic infectious disease, so anaemia
of inflammation may contribute significantly. "

12. Etiological factors for anemia in TB
 Anemia of chronic disease
 Iron deficiency
Nutritional deficiency
Secondary to chronic blood loss

14.  Serum ferritin level is unreliable marker for Iron
deficiency anemia in patients with TB.
 Serum Iron & TIBC observed to be low
 Erythropoietin level low in TB

15.  The inflammatory process in TB results in increased
serum ferritin inspite of decreased iron stores.
 Higher RDW (normal 6-8 µm) similar to IDA.

16. Observations suggest that Fe supplementation in mild to
moderate anaemia associated with pulmonary tuberculosis
accelerated the normal resumption of haematopoiesis
in the initial phases by increasing Fe saturation of
transferrin.

17. Results: Of the 1245 patients included in the study, 86% were
anemic and 7% were sputum smear positive at two months of
anti-tuberculosis therapy.
• Anemic patients were three times more likely to have sputum
positive smear as compared to nonanemic patients at two months
(RR = 3.05; 95% CI 1.11–8.40) p = 0.03.
• The risk for sputum positive smear results increased with
severity of anemia (P for trend ,0.01).

18.  Folate deficiency
 Vitamin B12 deficiency
 Hypoplastic or aplastic anemia
 Pure red cell aplasia
Etiological factors for anemia in TB

19.  Drug induced anemia
marrow aplasia
hemolysis
 Primary hematological disorder with TB
 Sideroblastic anemia
 Hemolytic anemia

20. LEUCOCYTE CHANGES
 Mild leucocytosis with increased myelocytes &
metamyelocytes.
 In Pulmonary TB leucocytosis more frequent than
leucopenia.
In dissemeinated TB leucopenia is significantly higher
than leucocytosis.

21.  Recent infection with TB shows peripheral blood
lymphocytosis (CD 4 &CD 8 T ).
 Lymphopenia (CD 4) is most common in pulmonary
TB ( granuloma formation)
 No change in B lymphocyte count.
 The pleural effusion & ascitic fluid samples contained
T- lymphocytes (majority CD 4).

24.  Neutropenia is mc in disseminated TB.
 Pelger –Huet anomlay seen .
 Monocytosis & monocytopenia.
 Basophilia with dissemenated TB
 Hypereosinophilic syndrome with organ damage.
 Isolated eosinophlia .

25. 1
• Leucocytosis due to increased myelopoiesis
• Bone marrow & peripheral blood show leukaemoid
reaction.
2
• Neutropenia due to hypersplenism , increased
demand , excessive margination of neutrophils.
• Cell mediated autoimmune mechanism.
3
• Lymphocytopenia due to continuous recruitment of
CD 4 T-lymphocyte for granuloma formation.
• Recent infetion shows lymphocytosis

27. PLATELET ABNORMALITIES
 Mild thrombocytosis : Acute phase response
- Increased thrombopoiesis
- Inflamatory cytokine (IL- 6).
 Thrombocytopenia is more common in disseminated
TB , throbocytosis is more common in pulmonary TB.

28.  Isolated thrombocytopenia occasionally seen in TB…..
???
-Immune mediated mechanism (GP Ib&IX com)
-Antiplatelet antibodies (circulating &bound)
-Platelet associated immunoglobulin(IgG)

29.  Thrombotic thrombocytopenia seen with pulmonary
& extra pulmonary TB due to increased pro coagulant
activity of IL -1 on endothelial cell.

30. PANCYTOPENIA
 It is mostly associated with underlying hematological
disease.
 Rare in patients with TB & may occasionally associated
with drug toxicity.
 Disseminated TB associated with Splenomegaly ,
which imparts pancytopenia.

31.  Pancytopenia may resolve after splenectomy s/o
hypersplenism may be the cause of pancytopenia .
 Other causes
Haemophagocytosis
Hypocellularity of marrow

32. HLH should be considered as a differential diagnosis in
patients with tuberculosis who
present with cytopenias, organomegaly, and
coagulopathy
Tuberculosis-associated HLH with a favorable
outcome
following early initiation of antitubercular therapy
(ATT).

33. COAGULATION ABNORMALITIES
 Disseminated intravascular coagulation (DIC) is seen
in pulmonary TB and disseminate TB .
??
 Reduced activity of Anti Thrombin -3.
 aPTT, TT increased.
 Early ATT institution shows significant survival.

34. DECREASED ANTI THROMBIN

35.  Acquired Factor V deficiency ,
 Transient protein S deficiency ,
 Increased C –reactive protein ,
 Deep vein thrombosis ,
 Transient thrombasthenia

36.  Bone marrow emboli in miliary TB ,
 Budd chiari syndrome in hepatic TB
 Portal vein thrombosis in abdominal TB.

37. BONE MARROW CHANGES
 Both localised and disseminated TB can lead to a
spectrum of histopathological changes in in bone
marrow.
Typical caseating granuloma formation,
non caseating granulomas ,
marrow hypoplasia , red cell aplasia , megaloblastosis ,
haemophagocytosis , necrosis of marrow .

38.  In most patients with pulmonary TB , the marrow
shows “reactive changes” with increased granulocytic
hyperplasia with mild to moderate plasmocytosis is
seen less frequently in miliary TB .

39.  Myeloid hyperplasia
 Plasmacytosis
 Megaloblastoid maturation
 Hypoplasia or aplasia

40.  Haemophagocytosis
 Caseating and non-caseating granulomas
 Bone marrow necrosis
 Myelofibrosis
 Increased iron stores

42. Results: The peripheral blood findings seen were anemia, raised
ESR, leukocytosis, neutrophilia, lymphocytosis,
eosinophilia, leucopenia, thrombocytosis and
thrombocytopenia.
The bone marrow changes seen were hypercellularity , myeloid
hyperplasia , erythroid hyperplasia with
megaloblastic changes and reactive plasmacytosis.
Another interesting finding in bonemarrow was presence of
granulomas which were seen in 5% of cases of which 1 case

45. DRUG INDUCED CHANGES
 Many of the abnormalities seen with TB can also be
induced by the ATT , it makes the diagnosis difficult in
a patient initiated on therapy.

46.  Autoimmune hemolytic anaemia
R , PAS , INH
 Megaloblastic anaemia
PAS (malabsorption of vit B 12)
 Sideroblastic anaemia
INH , Cycloserine , Pyrazinamide

47.  Pure red cell aplasia
INH (Immune mediated )
 Agranulocytosis
Thioacatazone , PAS , Streptomycin
 Autoimmune thrombocytopenia
Rifampicin , INH , PAS

48.  Aplastic anaemia
Streptomycin , PAS
 Disseminated intravascular coagulation (DIC)
INH (Factor XIII deficiency )
Rifampicin (induction of cyto P -450 )
PAS (hypothrombinemia )

50. Pure red cell aplasia (PRCA) is a rare complication of
treatment with isoniazid mainly observed in adults.
We report two siblings who had anemia caused by PRCA
during administration of isoniazid.
• On discontinuation of isoniazid, the anemia
resolved rapidly.
• PRCA should be considered as a possible cause of
unexplainedanemia during isoniazid therapy in children.

51. • The mechanism of Isoniazid induced SA is an inhibition of
the δ-aminolevulinate synthase-2 resulting in a
depletion of haem synthesis.
• Pyridoxine acts as a co-factor in synthesis of δ-
aminolevulinate,and is inhibited by Isoniazid
.Substitution of pyridoxine is recommended

52. Thrombocytopenia is a serious side effect
occurs mostly due to rifampicin (RIF).
Drug binds noncovalently to membrane
glyco proteins to produce compound epitopes or
induce conformational changes for which
antibodies are specific .
• There are very few reported cases of
thrombocytopenia due to isoniazid

53. Conclusion
Focal & Disseminated TB causes hematological
changes.
Hematoligical changes are reversible with early
diagnosis and treatment of tuberculosis.
The wide spectrum of drug-induced hematologic
syndromes is mediated by a variety of mechanisms,
including immune effects, interactions with enzymatic
pathways, and direct inhibition of hematopoiesis.

55.  Next seminar on 05/08/2016
BLOOD SUPPLY OF LUNG – Dr. Satish
COAL WORKERS PNEUMOCONIOSIS
– Dr .Vedaranya