Pancytopenia

Pancytopenia is defined as a reduction in all three formed elements of the blood: erythrocytes, leukocytes, and platelets in peripheral blood and involves anaemia, leucopenia, and thrombocytopenia. Pancytopenia has symptoms of Bone Marrow Failure Syndrome (anaemia, recurrent infection and bleeding).

auses of Pancytopenia:
1. Decreased production by the marrow: two major subsections exist: Aplasia or hypoplasia of the marrow. Infiltration of the marrow, by a large variety of pathologies.
! primary blood disease myeloma, leu!emia, myelofibrosis and storage diseases !secondary displacement of normal hemopoietic elements" breast, thyroid, !idneys, prostate metastasis".

#. $eripheral destruction or se%uestration" of all the blood cells. &he comments is hypersplinism '. Destruction of blood cells in the marrow, prior to release into the circulation. &he commonest causes are: megaloblastic anemia, myelodysplasia, hemophagocytic syndrome.

lassification of Pancytopenia: according to bone marrow cellularity "# $ypocellular Bone Marrow ( most common manifestation of this is %plastic anemia.
Idiopathic )*+, ac%uired, and hereditary rare: eg. ,anconi-s anemia"

auses of ac&uired aplastic anaemia: .adiation /hemotherapy /hemicals e.g. 0en1ene" 2iruses ( 3I2, $arvovirus 014 5rythrovirus", human herpesvirus ) 3326 )", 502, 3epatitis viruses most commonly hepatitis 0" $aroxysmal 7octurnal 3emoglobinuria defect at the level of stem cells" flow cytometry". 'rugs:

Antibiotics /ytotoxics Anti thyroid medications 7on steroid medicines Anti6inflammatory drugs 3igh blood pressure medicines (ab finding of aplastic anemia:
8ow numbers of all formed blood cells Pancytopenia). 7ormocytic normochromic anemia may be macrocytic. 2ery low reticulocytes count, 0one marrow examination will reveal very few or no hematopoietic cells aspiration 9 biopsy : 3ypocellular : aplastic bone marrow", and replacement with fat. &ests for underlying cause viral titers"

)# ellular Bone Marrow: %) Primary causes:

I.

;yelodysplastic <yndromes ;yelofibrosis the fibrosis is a secondary late event" 8eu!emia:8ymphoma ;etastatic tumors to the bone

II. III. I2.

B) Secondary causes:
*# Megaloblastic anaemia# **# *ncreased peripheral utili+ation or destruction: 3yperslenism /ommonest cause is chronic liver diseases". <ystemic lupus erythematosus <85" haracteristics of hyperslenism: <plenomegaly may be normal si1e". .eduction of cellular elements of blood e.g. monocytopenia, bicytopenia or pancytopenia. 3yperplasia of bone marrow corresponding with cytopenias. /orrection of cytopenias by splenectomy. ***# *nfection: =ala6a1ar 2isceral leishmaniasis) Disseminated tuberculosis ;alaria
;egaloblastic anemia especially in younger children" and infections such as enteric fever, malaria, !ala6a1ar and bacterial infections can be common causes of pancytopenia in the developing countries. /linically, a child presenting with pancytopenia should be evaluated for possibility of either a bone marrow failure syndrome or acute malignancy, particularly when associated with lymphadenopathy or visceromegaly.

'iagnosis of pancytopenia depend on: % thorough history and physical e,amination are always re&uired# (aboratory in-estigation .adiology

Pancytopenia Symptoms:
$ancytopenia sufferers display a number of abnormalities apart from low blood cell and platelet count.
'

/he ma0or Pancytopenia signs and symptoms are:

%naemia Fatigue $allor Palpitation Shortness of Breath .ecurrent, resistant to ttt 1ose Bleeding ;enorrhagia Petechiae

*nfection Bleeding

*n-estigation of pancytopenia:
1. Peripheral blood e,amination: to chec! any reduction in blood cell coun #. .eticulocytic count. '. 2,amination of bone marrow : &he bone marrow examination consists of both an aspirate and a trephine biopsy. %spiration biopsy of the bone marrow is done for the evaluation of unexplained cytopenias and malignant conditions li!e leu!emia or staging of a neoplasm. /rephine biopsy is usually performed when there is hypoplasia or aplasia on aspiration dry tape". /rephine biopsy also permits examination of histology and evaluation for: /ellular infiltration 0lasts ,eatures of ;D< .eticulin stain to visuali1e reticular fiber in myelofibrosis" 3ther laboratory tests:

8,&s.
>

/oagulation profile, bleeding time, fibrinogen, and D6dimer. <erum 01# and folate.

Specific testing pinpoints diagnosis in the following conditions: 1. *mmunophenotyping: (eukaemia, lymphoma , $73 /D??, /D?4" )# %ntibodies:

Direct antiglobulin test for immune6mediated hemolytic anemia.

Infections : /;2 infection: serum Ig; and Ig@, 5pstein60arr: serum monospot antibodies, 8eishmaniasis and other rare infections: blood and bone marrow culture. 4# /umor markers in secondary metastasis. 5# ytogenetic study for common translocations Acute leu!aemia".

.adiology: Abdominal ultrasound scan or /& scan of the abdomen is indicated to evaluate for splenomegaly. /hest A ray may reveal tumour masses responsible for pancytopenia e.g., carcinoma, thymoma". In cases where metastatic infiltration of the bone marrow is suspected, thyroid ultrasound or breast imaging may also be appropriate.

Step-by-step diagnostic approach

%cute leukemia (%M(,%(() A88 Age /ommon in children 0leeding 8ess 8ymphadenopathy ;ore 3epatosplenomegaly ;ajority /7< ;ore meningitis" @um hypertropgy 6666 &esticular 1*6#*+ involvement /ytochemical stain ;yeloperoxidaes 6ve <udan blac! (ve $eriodic acid <chiff &erminal deoxynucleotideyl transferase &d&"B 0last morphology 7o Auer rods ,lowcytometry 0: /D 14,/D#* &: /D ',C

A;8 adult ;ore 8ess 8ess less /ommon 8ess Bve Bve 6 ve 6 ve Auer rods /D 1', /D''

hronic myeloid leukemia: C*+ of patients are asymptomatic at the time of diagnosis 3igher among men than women at >*years or older Pathophysiology: D $hiladelphia chromosome 4:##" in 67897: D 0/.6A08 protein junction fusion gene located in the $hiladelphia $h" chromosome." linical manifestation: 1. #. '. >. ?. ). C. E. Dragging pain in left hypochondrium huge spleen" <titching pain due to splenic infarction pallor manifestation of anemia" 0one aches <ternal tenderness" ,ever 9 sweating not due to infection" 0rusing 9 bleeding tendency gingi-ae most common" <ymptoms of leucocytosis e.g headache, focal neurological deficits" 8ymphadenopathy with blast crisis 9 0; failure. C

/hree Phases of M(: 1. /hronic phase: #. Accelerated phase: ;arrow or blood blasts between 1*6#*+. 8asts several months before becoming blastic. '. 0last phase: #*+ blasts in blood or marrow indistinguishable from acute leu!emia. &he cause of death in majority of cases. *n-estigation: ") Blood picture: a. &8/ is usually ; <7,"79=l > some times ;<77?"79 =l# b. It is mainly myelocytes, promyelocytes and mature neutrophils with eosinophilia, basophilia. c. ;yeloblasts F 1*+ increase in blast crisis". d. $latelets tends to be raised. e. 7ormocytic normochromic anemia. #" 8eu!ocyte al!aline phosphatase decreased" '" G uric acid, G8D3 >" Bone marrow shows hypercellularity due to myeloid hyperplasia blasts F?+ in chronic phaseH ?614+ in accelerated phaseH I#*+ in blast crisis"H trephine biopsy is useful to assess marrow fibrosis. ?" =aryotypingH chromosomal testing: present of $hiladelphia chromosome 4:##" in marrow precursor cells in 4?+. )" /;8 is now diagnosed using $/. to reveal the abnormal fusion gene. (eukemoid reaction G &8/J #?.***6 up to ?*.***" simulating leu!emia. It may be myloid reaction hemorrhage, hemolysis, 0; metastasis or suppurative infection". It may be lymphoctic reaction /;2, I;7 and &0" riteria: 1" &here is a cause. #" Immature cells never J ?+ '" $latelets are normal >" .0/s are normal ?" 0; proliferation normal" with no increase of blasts. )" 8eu!ocytic al!aline phosphatase is high.

(eukoerythroblastic reaction E

&he presence of immature K0/s shift to left" and nucleated .0/s normoblasts" in peripheral blood due bone marrow infiltration. hronic (ymphocytic leukemia Adults J ?* years, male J females Accumulation of mature appearing lymphocytes in blood, 0; 9 lymphoid tissue. haracterised by: ;ostly, the cell of origin is 0 lymphocytes. Infiltration of lymphoid organs liver, spleen 87 9 0;" .edused immunoglobulins infection Abnormal immune reaction auto antibodies. linical manifestation: 1. #. '. >. ?. ). <ome cases are symptomatic. @eneralised lymphadenopathy 3epatosplenomegly. Anemia in advanced cases, autoimmune hemolytic anemia. 0leeding tendency. .ecurrent infections reduced immunoglobulins"

*n-estigation:
1" 0lood picture: a. Increase &8/ with lymphocytosis the absolute lymphocyte count may be up to '**x1*4:l or more". b. 7ormocytic normochromic anemia. c. 8ow platelets with marrow failure or immune destruction. #" 0lood film:C*644+ of white cells mature lymphocyte. <mudge or smear cells also present. '" /oombLs test positive autoimmune 3.A. may occure, warm A0" >" Immunoglobulins are low or normal. ?" *mmunophenotyping by ,low cytometry: <hows that the lymphocyte are 0 cells /D14", cells are also /D?9/D#'Bve. )" Bone marrow aspiration: 8ymphocytic replacement of normal marrow. C" 8ymph node biopsy