PANCYTOPENIA Flashcards
Define pancytopenia.
def. of BLOOD cells of ALL lineages
Is pancytopenia a dx?
Does it always mean bone marrow failure?
NO
-NO
Describe the maturation of a red cell.
- Pronormoblast
- Early normoblast
- Intermeidate normoblast
- Late normoblast
- Reticulocyte
- Mature Red cell
Describe the sequence of neutrophil maturation.
Myeloblast Promyelocyte Myelocyte Metamyelocyte Band neutrophil Segmented neutrophil
Describe the seq. of platelet maturation
Myeloid stem cell
Megakaryoblast
Megakaryocyte
Why may pancytopenia occur?
- INCREASED DESTRUCTION
2. REDUCED prodn
What causes reduced prodn?
- bone marrow failure (INHERITED syndromes)
- acquired (Iary or IIary)
Why may bone marrow failure occur?
- cancer pre-disposition
- impaired haemopoiesis
- congenital anomalies
all d.t DEFECTS in DNA repair/ribosomes
How may inherited marrow failure present in an individual?
(rare)
- short
- skin problems
- radial ray abnormalities
- hypogenitilia
- endocrinopathies
- GI defects
- renal and hemato issues
Name an inherited marrow failure syndrome.
Fanconi’s Anaemia
What are radial ray abnormalities?
- range of upper limb anomalies
- –radial HYPOPLASIA> radial aplasia
What skin anomalies may occur?
cafe au lait spots
What hemato problems arise d.t inherited bone marrow failure?
- macrocytosis, FOLLOWED by thrombocytopenia, then neutropenia
- —risk of APLASIA (84% by 20 years)
- —-risk of leukaemia (52% by 40 years)
Why may hemato problems arise?
- d.t the inability of the blood cells to CORRECT their inter-strand cross-links (DNA damage)
Name acquired PRIMARY bone marrow failure.
- idiopathic aplastic anaemia
- Myelodysplastic syndromes
- Acute Leukaemia
Wht occurs as the pathophysiology of idiopathic APLASTIC anaemia?
Only manifestation?
- multipotent MYELOID stem cells are suppressed d.t T-cell overactivity
- –only erythroid progenitors are affects
—anaemia is the only manifestion
What are some myelodysplastic syndromes?
- DYSPLASIA (d.t DISORDERED development) !
- HYPERCELLULAR marrow
- INCREASED APOPTOSIS of progenitor and MATURE cells (ineffective haemopoiesis)
What can the MDS evolve into? WHY?
AML
—because the abnormal stem cell clone in the marrow is GENETICALLY unstable and PRONE to the acquisition of ADDITIONAL mutations
What is the pathophysiology of myelodysplastic syndrome?
bone marrow is partly or wholly replaced by CLONAL progeny of multipotent stem cell that CAN differentiate into red cells, platelets and granulocytes
—-BUT in INEFFECTIVE and DISORDERLY way
What is seen as a consequence of MDS, in a marrow sample?
- marrow that is HYPERCELLULAR/ normocellular
- but peripheral blood show one or more cytopenias
What cells would you expect to see in a case of MDS, in the marrow?
- megaloblastoid erythroid precursors (resembles megaloblastic anaemia) —ringed sideroblasts
- small megakaryocytes with SINGLE/ small nuclei OR multiple seprate nuclei
- granuocytes with abnormal granules
Why can acute leukaemia cause pancytopenia?
- proliferation of abnormal cells from leukaemic stem cells
- fails to differentiate/mature into NORMAL cells
—prevent NORMAL stem cell development; hijacking the haemopoietic NICHE
and marrow microenv.
What induces bone marrow failure?
(IIary)
1. Drugs
- B12/ Folate def.
- Infiltrative- Non-hemopoietic MALIGNANT infiltration/ lymphoma
- others: Viral (HIV)/ storage diseases
What drugs cause marrow failure?
CHEMO
Chloramphenicol
Alcohol
—known to cause APLASIA
What incr.-destruction, results in pancytopenia?
- Hypersplenism
What occurs with hypersplenism?
- incr. splenic pool
- incr. destruction that EXCEEDS bone marrow capacity
What causes high rate of sequestration in hypersplenism?
those with a red cell mass of 40%
—–mean transit time for red cells will be SLOW !
Does splenic size alone, correlate with hypersplenism?
NO
—-but splenomegaly CAN potentially result in hypersplenism
Causes of HYPERSPLENISM.
- splenic congestion (portal hypertension, CHF)
- Systemic diseases (RA- Felty’s)
- Haematological diseases (Splenic lymphoma)
Clinical fts of pancytopenia?
- lack of circulating blood cells
- anaemia+ neutropenia+ thrombocytopenia
What are the symptoms of anaemia?
- fatigue
- SOB
- CVS compromise
Thrombocytopenic fts?
- bleeding (purpura/ petechiae/ wet bleeds
Ivx for pancytopenia?
- FBC, blood film
- B12/ folate; LFTS; Virology; autoantibody tests)
- bone marrow examination
- special test (cytogenetics/ chromosome fragility)
With suspected Fanconi’s anaemia, what ivx is done?
- cytogenetics
When is a hypercellular marrow seen?
- MDS
- B12/Folate def. (late maturation FAILURE+ Early proliferation+ apoptosis)
- hypersplenism
What supportive treatment can be given for pancytopenia?
- Red cell transfusions
- platelet transfusions
- neutrophil transfusions (though NOT routine)
- antibiotic prophylaxis/ treatments (anti-fungals/ antibacterials)
What is a possible rx for hypersplenism?
SPLENECTOMY
—–not ALWAYS the case
If the pt has a CONGENITAL bone marrow disorder, what should be given as a treatment?
- bone marrow transplantation!
How to manage idiopathic aplastic anaemia?
by immunosuppression
