Figure 1: Presence of large platelets in peripheral (EDTA) blood smear (left top), increase of clustered enlarged megakaryocytes in a normocelluar ET bone marrow with stainable iron (left bottum). Local increase of erythropiesis (bold arrows) in areas of loose clustered pleomorphic megakaryocytes in patients with essential thrombocythemia: ET bone marrow picture [1]
Figure 2: ET (left upper), ET/PV (left right), and PV (left bottum) bone marrow features in ET and PV patients. Pleiomorphic megakaryocytes in ET (upper panels) have less hyperlobulated nuclei as compared to PV (left bottum). Dense clustered pleiomorphic megakaryocytes in PV/RF (right bottum) in advanced PV show dysmorphic nuclei [1]
Figure 3: Correlation of erythrocyte counts and erythrocyte volume or red cell mass in 5 ET and 13 PV patients. Two ET patients with borderline increased RCM had erythrocyte counts above 5.8x1012/L associated with a typical PV bone marrow histology and should in fact be diagnosed as PV. Erythrocyte count at a cut off level of 5.8x1012/L differentiates between ET and PV even in iron deficient state of PV remission after phlebotomy
Figure 4: Case 2 in Table 7 with a 10 to 5 years history of stable JAK2V617F positive ET disease and ET bone marrow picture in 2006: normocellular ET stage 1 showing a typical ET bone marrow picture with cellularity of 60% due to slight increase of erythropiesis (upper panels). Case 6 in Table 7 with ET and a PV bone marrow in 1997, who developed PV seven years later in 2004 with a good response to interferon in 2005 (lower panels)
Figure 5: Case 7 in Table 7 presented with rapid onset JAK2V617F positive erythrocythemic PV with a typical PV bone marrow picture in 2005 carrying homozygous JAK2V617F mutation on repeated testing. The erythrocyte counts were far above 6x1012/L and remained above 6x1012/L at time of hematological remission of PV for several years by phlebotomy alone on top of low dose aspirin
Figure 6: Rapid onset trilinear JAK2V617F homozygous positive PV Case 9 in Table 7 with a typical trilinear PV bone marrow picture complicated by bleeding, poor response to pegylated interferon indicating the need to treat with hydroxyurea on top of low dose aspirin resulting in eliminating the thrombo-hemorrhagic diathesis and significant imporovement of quality of life during long-term follow-up (2006-2013)
Figure 7: 65 years old man with RBC 5.37x1012L, HB 15.8 g/dL, MCV 89, WBC 12.0 x10/9/L, Plts 517x109L, LDH 600 UI/L and JAK2V617F mutation (allele burden: 20% on peripheral blood). Diagnosis PV according WHO-ECMP (left). 55 years old woman with MPL515-positive normocellular ET with normal values for hemoglobin, hematocrit, leukocytes and platelet around 1000x109/L. Dr. Campr: small medium, large and giant megakaryocytes with staghorn-like hyperlobulated nuclei (right)
Figure 8: JAK2 wild type ET carrying the MPL515 mutation with enlarged and giant mature megakaryocytes with loose clusters of hyperlobulated, "stag-horn" hyperlobulated nuclei. Case 1 and 2, Dr. Vannucchi, upper panels. Case 3, Dr. Vannucchi lower panels
Figure 9: JAK2 wild type, MPL515 mutated ET with enlarged and giant mature megakaryocytes with loose clusters of hyperlobulated, "stag-horn" hyperlobulated nuclei. Case 4, Dr. Vannucchi, upper panels. Case 5, Dr. Vannucchi, lower panels
Figure 10: Case of JAK2 wild type MPL515 mutated ET with clustered large and giant megakaryocytes and increase of reticulin fibrosis grade 2 (RF 2). Such increase of RF 2 in a normocellular bone marrow is not seen in JAK2V617F mutated ET and PV, and also not in JAK2 wild type PMGM(Figures 11 and 12) and CALR-MGM (Figures 13 and 14)
Figure 11: Third MPN entity presenting with JAK2 wild type ET associated with prefibrotic primary megakaryocytic and granulocytic myeloproliferation (PMGM, colour picture), which is characterized by a hypercellular bone marrow due to dual myeloproliferation of granulopoiesis and dense clustered enlarged immature dysmorphic megakaryocytes with bulky (bulbous) hyperchromatic nuclei (arrows), which are never seen in JAK2 wild type MPL515 mutated ET and also not in the prefibrotic JAK2V617F mutated ET. During long-term follow-up, reduction of platelet count to normal or near normal by treatment with hydroxyurea in 1994 followed by anagrelide from 1995 to 1998 the bleeding manifestations did not recur. After discontinuation of anagrelide in 1998 the patient remained asymptomatic, the platelet counts were between 600 and 800x109/L, which normalized after 8 years of follow-up. From 2001 to 2005 haemoglobin and hematocrit reached completely normal values
Figure 12: 37-years old woman (asymptomatic except fatigue) with JAK2 wild type hypercellular ET (anno 2006): platelets 1205 x109/L, Hb 12.5 g/dl, leukocytes 18 x109/L, borderline LDH, spleen size 13 cm on echogram (normal value <12cm) as the presenting features of primary megakaryocytic granulocytic myeloproiferation (PMGM, RF-1) diagnosed according ECMP criteria but not meeting the 2008 WHO criteria for primary myelofibrosis (PMF). In 2015 this case proved to be calcireticulin (CALR) mutated
Figure 13: Bone marrow features in newly diagnosed calreticulin (CALR) mutated essential thrombocythemia (ET, left) and early stage myelofibrosis (MF, right) Left: Clinical case of JAK2/MPL negative and calcireticulin (CALR) positive ET who presented with normal vlaues for hemogobin, hematocrit and erythrocytes, platelet count of 1832x109/L and slight splenomegaly (16 cm lenght diameter on echogram). Bone marrow histology is hypercellular with relative decrease of erythropoisis, dense cluster of immature megakaryocytes with hypolobulated nuclei consistent typical PMGM and no increase of reticulin fibrosis (Table 5) Right: Clinical case of CALR positive myelofibrosis (MF): hemoglobin 11.2 g/dL,hematocrit 0.33, leukocytes 9.2x109/L, platelets 347x109/L, LDH 1393 U/l, and the presence of tear drop erythrocytes, poikolocytosis and polychromasie in a peripheral blood smear, and hypercellular bone marrow with relative decrease of erythropoisis, dense cluster of immature megakaryocytes with hypolobulated nuclei consistent with PMGM, and reticulin fibrosis (RF) grade 2.The marrow histology features similar to WHO-defined primary myelofibrosis (PMF) and WHO-ECMP-defined PMGM or CALR-MGM, but distinct from JAK2V617F mutated ET and PV, and distinct from MPL515 mutated ET
Figure 14: A 67 year old man presented in 2015 with normocytic anemia (hemoglobin 5.2 mol/l, hematocrit 0.25 and erythrocytes 3.1x1012/L, platelets 265x109/L, leukocytes 6.5x109/L) weight loss from 84 to 71 kg in the last 2 years, minor fatigue, no sweatings, asymptomatic splenomegaly and dense clustered dysmorphic megakaryocytes, reticulin fibrosis grade 3 to 4, which was diagnosed as JAK2 wild type calcireticulin (CALR) mutated MF without a history of ET
Figure 15: 2015 WHO-ECMP Myeloproliferative Neoplasms Classification and Transitional states
A. The 1980 RCP major (A) and confirmative (B) criteria for prefibrotic ET [1]
A1 Persistent platelet count in excess of 400x109/L.
A2 Increase and clustering of enlarged megakaryocytes in bone marrow biopsy.
A3 No or slight increase of reticulin fibers (RF 0 or RF 1)
B1 Presence of large platelets in a peripheral blood smear
B2 Absence of any underlying disease for reactive thrombocytosis and normal ESR.
B3 No or slight splenomegaly on palpation or scan (<15 cm)
B4 Increase of LAP-score and no signs of fever or inflammation
Exclusion criterion
Ph+ chromosome and any other cytogenetic abnormality in blood or bone marrow cells
B. The 1980 RCP major (A) and minor (B) criteria for prefibrotic PV [1]
A1 Raised red cell mass. Male >36 ml/kg, female >32 ml/kg consistent with erythrocyte count of >6x1012/L (Dameshek 1940 [18])
A2 Absence of primary or secondary erythrocytosis by clinical and laboratory tests.
A3 Slight, moderate or marked increase in bone marrow biopsy of clustered, enlarged pleomorphic megakaryocytes with hyperlobulated nuclei and moderate to marked increase cellularity of megakaryopoiesis/erythropoiesis or typically trilinear mega-erythro-granulopoiesis.
B1 Thrombocythemia, persistant increase of platelet >400x109/L
B2 Leukocytosis, leucocyte count >109/L and low erythrocyte sedimentation rate (ESR)
B3 Raised leukocyte alkaline phosphatase (LAP) score >100, absence of fever or infection
B4 Splenomegaly on palpation or on isotope/ultrasound scanning
A1+ A3 plus one of B establishes PV and excludes any variant of erythrocytosis
C. Grading of bone marrow reticulin fibrosis (RF) and grading of myelofibrosis (MF)[5-8]
Grading reticulin
fibrosis (RF)		 Grading MF Thiele, et al. Description of reticulin fibers (RF) and reticulin/collagen fibers (RCF)in myelofibrosis (MF) [22] as a secondary event in myeloproliferative neoplasms (MPN)
Normal
RF-0		 N
MF 0		 No reticulin fibers, occasional individual fibers or focal areas with tiny amount of reticulin fiber network
Slight increase
RF 1		 +
MF 0		 Fine reticulin fiber network throughout much of section and no course reticulin fibers
Moderate increase RF 2 + +
MF 1		 Diffuse fine reticuline network with focal collections of thick course reticulin fibers and no collagenisation
Marked increase
BM dry tap RF 3		 +++
RCF = MF 2		 Diffuse and dense increase in reticulin with extensive intersections, and presence of collagen fibers and no or minor osteosclerosis
OS Dry tap
RF 4		 Sclerotic
RCF&O = MF 3		 Diffuse and dense reticulin with coarse bundles of collagen associated with significant osteosclerosis (O)
Table 1: The 1980 Rotterdam Clinical and Pathological (RCP) criteria for Essential Thrombocythemia (ET) and Polycythemia Vera (PV)[1]
Clinical and molecular criteria Bone marrow pathology criteria (WHO)
ET Normocellular ET
1. Platelet count of >350 x109/l and the presence of large platelets in a blood smear
2. Presence of JAK2-V617 F mutation
3. Normal erythrocytes, haemoglobin (Hb) and hematocrit (ht)		 Predominant proliferation of enlargedmature megakaryocytes with hyperlobulated nuclei and mature cytoplasm, lacking conspicuous morphological abnormalities. No increase, proliferation or immaturity of granulopoiesis or erythropoiesis.
Reticuline fibrosis (RF) 0 or 1
Prodromal PV ET with features of PV
1. Platelet count of > 350 x109/l and normal ht male <0.51, female <0.48, normal erythrocyte <5.8x1012/L is mandatory.
2. Presence of JAK2-V617F mutation
3. Low serum EPO level and/or increased LAP score
4. Spontaneous EEC.		 Increased cellularity with due to increased erythropoiesis or trilineage myeloproliferation (i.e. panmyelosis). Proliferation and clustering of small to giant (pleomorphic) megakaryocytes.
Absence bone marrow features consistent with congenital polycythemia and secondary erythrocytosis. RF 0 or 1
Prefibrotic hypercellular ET ET.MGM
1. Platelet count of >350 x109/l,
2. No signs of leuko-erythroblastosis
3. Slight or moderate splenomegaly on ultrasound
4. No anemia with hb and ht in the normal low normal range: hb>13g/dl
5. Presence of JAK2-V617 F mutation
6. No preceding or allied CML, PV, RARS-T or MDS.
-------------------------------------------------
ET stage 4, borderline anemia and LDH↑
ET stage 5 Hb<12 g/dL, LDH↑↑, CD34+
-------------------------------------------------
ET stage 6, Post-ET MF (2008 WHO)		 Hypercellular ET due to chronic megakaryocytic and granulocytic myeloproliferation (ET.MGM) and normal or reduced erythroid precursors.
Loose to dense clustering of more pleiomorphic megakaryocytes with hyperploid or clumpsy nuclei (not or some cloud-like).
Prefibrotic: RF- 0/1, MF-0, no/minor splenomegaly
--------------------------------------------------------
Early fibrotic ET:RF 2, MF 1, splenomegaly no/minor
Fibrotic ET : RF3, RCF or MF2, overt splenomegaly
------------------------------------------------------------
Post-ET MF: RF3/4, or MF-2/3 (2008 WHO PMF)
Table 2: WHO and European clinical molecular pathological (WHO - ECMP) criteria for diagnosis and classification of prefibrotic JAK2V617F mutated prefibrotic ET [15,25]
Clinical and molecular criteria Bone marrow pathology criteria (WHO)
Major
Prodromal PV (ET stage 2). Hematocrit upper limit of normal: Ht: 0.45 to 0.51 in male and 0.43 to 0.48 in female), erythrocytes <5.8x1012/L
PV
A1. Hematocrit >0.51/>0.48 in male/female, erythrocytes >5.8x1012/L
A2. Presence of heterozygous or homozygous JAK2V617F or JAK2 exon 12 mutation
A3. Low serum Epo level
Minor
B1. Persistent increase of platelet count: grade I: 400-1500, grade II: >1500 x109/L
B2. Granulocytes >10 x109/l or Leukocytes >12 x109/l and/or raised LAP-score in the absence of fever or infection
B3. Splenomegaly on palpation or on ultrasound echogram (>12 cm length in diameter).
B4. Spontaneous endogenous erythroid colony (EEC) formation (optional)		 PV. Bone marrow pathology: increased cellularity (60-100%) due to trilinearincrease of erythropoiesis, megakaryopoiesis and granulopoiesis and clustering of small to giant (pleomorph) megakaryocytes with hyperlobulated nuclei.
Absence of stainable iron. No pronounced inflammatory reaction (plasmacytosis, cellular debris)
Erythrocytosis. Increase of erythropoiesis, normal granulopoiesis and megakaryocytes of normal size, morphology and no clustering in primary/secondary erythrocytosis.
Grading of reticulin fibrosis (RF) and myelofibrosis (MF)
Erythrocythemic stage: A1 and P1
Prefibrotic: RF-0/1 = MF-0
Early fibrotic: RF-2 = MF-1
Fibrotic: RCF 3 = MF-2
Post-PV MF: RF 4 = MF-3
On top of WHO bone marrow histology: ECMP criteria for staging of early, overt, and advanced PV
A0, A2, B1 establish early PV (mimicking ET) PV ECMP stage 0, or masked PV
A1, A2, and none of B establish polycythemic PV ECMP stage 1
A1, A2, and one or more of B establish classic and advanced PV ECMP stage 2 and 3
A2, B3 and P1 detect masked ET or PV: primary myeloproliferative disease (PMD)
A3 and B4, bone marrow smear and JAK2V617F mutation is an important research option.
Table 3: WHO-ECMP criteria for the diagnosis of PV and erythrocytoses [15,25]
Clinical and molecular (CM) JAK2 wild type ET Bone marrow pathology (P) criteria (WHO)
1. Platelet count >350x109/L and presence of large platelets in blood smear
2. Hemoglobin, haematocrit and erythrocyte count in the normal range
3. Presence of MPL515 mutation and JAK2 wild type
4. Normal serum EPO
5. Normal LAP score and CD11b expression
6. No or slight splenomegaly
7. No leukoerythroblastosis
8. No preceding or allied CML, PV, RAS-T or MDS		 P1. Proliferation of large to giant mature megakaryocyte with hyperlobulated, staghorn-like nuclei in a normocellular bone marrow (<65%)
No increase of erythropoiesis, and no increase or immaturity of granulopoiesis or erythropoiesis, No or slight increase in reticulin RF 0/1
ET → MF
Increased reticulin fibrosis around dense clustered megakaryocytes in a normocellular bone marrow and reduced erythropoiesis. Follow-up data of RF and MF related to splenomegaly in MPL515 ET transltional states to MF are lacking. Grading of reticulin fibrosis (RF) and myelofibrosis (MF) is similar as described for PV
Table 4: 2014 WHO Clinical Molecular and Pathological (2014 WHO-CMP) criteria for the diagnosis of normocelular ET carrying one of the MPL515 mutations [15,25]. This entity is identical to 'true' ET as defined in 2002 by Michiels & Thiele [5].
Clinical (CM) criteria JAK2 wild type PMGM Pathological ECP criteria of CALR MGM
A1 No preceding or allied other subtype of myeloproliferative neoplasm PV, CML, MDS. The main presenting features is pronounced isolated thrombocythemia with platelet count around or above 1000x109/L
A2 Presence of CALR mutation and JAK2 wild type
C Clinical stages of CALR MGM
C1. Early clinical stage: Hb>12g/dL, slight to moderate splenomegaly, thrombocytosis around or above 1000x109/L, normal LAP score
C2. Intermediate clinical stage: slight anemia Hb<12 to >10 g/dL, decreasing platelet count, splenomegaly, increased LDH and definitive tear drop erythrocytes
C3. Advanced stage: anemia Hb<10g/dL, tear drop erythrocytes, increased LDH, increased CD34+ cells, pronounced splenomegaly, normal or decreased platelet counts, leucocytosis or leukopenia.

P1 Primary megakaryocytic granulocytic myeloproliferation (PMGM) and relative or absolute reduction of erythropoiesis and erythroid precursors. Abnormal dense clustering and increase in atypical medium sized, large to giant immature megakaryocytes containing bulbous (cloud-like) hypolobulated nuclei and definitive maturation defects


MF Grading reticulin fibrosis (RF), myelofibrosis (MF)
MF0 Prefibrotic CALR MGM, no reticulin fibrosis RF 0/1
MF1 Early fibrotic CALR MGM slight reticulin fibrosis RF2
MF2 Fibrotic CALR MGM increase RF grade 3 and slight to moderate collagen fibrosis
MF3 Advanced fibrotic CALR MGM with collagen fibrosis-osteosclerosis
The combination of A1 + A2 and P1 establishes CALR ET and various clinical stages (C1, C2,C3) related to the degree of myelofibosis (MF)
Table 5: 2016 WHO-CMP criteria for hypercellular ET associated with primary megakaryocytic, granulocytic myeloproliferation (PMGM) caused by calreticulin (CALR) mutations [15,25]. This entity has been defined as PMGM in the 1990 Bone Marrow Classification by Georgii, et al. [22] as the third distinct MPD entity.
Number Leukoc LAF Ery/Plasm BM BM BM Platelets Hb Ht Erythroc
  109/L score volume RF megakar cellularity 109/L mmol/l   1012 /L
A1 ETPV 10 183 31 / 41 N 1+ N 792 10.4 0.49 6.7
A2 ETPV 9 155   N 1+ N 887 10.0 0.51 6.0
A3 ET 8 109   1+ 2+ 2+ 911 8.9 0.47 5.4
A4 ET 9 101   1+     614 8.0 0.39 4.5
A5 ET 16 128 26 / 37 N 1+ N 939 8.3 0.40 4.4
A6 ET 7 139   N 1+ N 742 9.8 0.49 5.8
A7 ET 8 127   N 1+ N 567 9.5 0.46 5.2
A8 ET 10 38   1+ 2+ 1+ 875 8.8 0.43 4.9
A9 ET 10 103   1+ 1+ 1+ 690 8.8 0.45 5.5
A10 ET 11 60   N 1+ N 1440 8.6 0.43 4.7
A11 ETPV 13 113 32 / 43 2+ 2+ 1+ 1435 9.4 0.46 6.1
A12 PV 10 207 59 / 52 1+ 1+ 2+ 1932 11.1 0.56 6.5
A13 PV 28 193   N 2+ 2+ 1800 12.1 0.62 7.6
A14 PVT 13 236   2+ 2+ 2+ 952 8.3 0.45 5.6
A15 PVT 11 103   1+ 2+ N 636 7.7 0.39 5.4
A16 PV 17 243 45 / 38 1+ 2+ 2+ 1065 13.4 0.68 7.9
A17 PV 8 186 60 / 51 1+ 1+ 1+ 728 10.9 0.57 7.5
A18 PV 14 184 63 / 50 1+ 2+ 1+ 1035 12.2 0.64 7.1
A19 PV 16 219 50 / 40 1+ 2+ 2+ 1320 13.3 0.70 6.4
A20 PV 18 128 38 / 52 1+ 2+ 1+ 1300 11.9 0.65 7.6
A21 PV 13 170 43 / 37 2+ 2+ 2+ 1085 12.1 0.61 7.1
A22 PV 17 168 42 / 35 1+ 2+ 2+ 708 11.0 0.59 7.5
A23 PV 9 219 54 / 42 1+ 2+ 2+ 959 13.1 0.72 9.1
A24 PV 18 215 82 / 46 2+     609 12.5 0.66 9.9
B 1 PV   235 38 / 36 2+ 2+ 2+ 2975 5.3 0.32 4.4
B 2 ET 5 20 28 / 58 1+   2+ 699 8.3 0.42 4.0
B 3 PV 14 140 58 / 62 1+ 2+ 2+ 918 11.3 0.38 7.3
B 4 PV 23 140 44 / 51 2+ 2+ 2+ 2500 12.7 0.63 7.7
B 5 ET 18 118 30 / 38 1+ 1+ N 810 10.0 0.50 5.1
B 6 ET 9 123 28 / 37 1+ 1+ N 737 9.0 0.47 5.0
A= complicated by erythromelalgia and/or migraine-like atypical transient ischemic attacks, B= asymptomatic ET or PV, ET= essential thrombocythemia, PV= polycythemia Vera, PVT=PV after phlebotomy
Table 6: Peripheral blood and bone marrow data in 14 ET and 16 PV patients observed between 1975 and 1981, University Hospital, Dijkzigt, Rotterdam [1]
Case 1 2 3 4 5 6 7 8 9 10
Age, years. F /M 56/M 60/M 66/F 47/F 40/F 31/F 50/M 43/F 47/F 38/M
Platelets x109/L 575 814 544 553 425 576 397 405 924 384
JAK2V617F +/- +/- +/- +/- +/- +/- ++ +/- ++ ++
Serum EPO Normal zero decreased decreasd. nt. decreased. zero decreased zero zero
Leukocytes x109/l 6.7 5.3 12.9 8.2 6.1 6.2 7.3 14.3 13.1 8.0
LAP score (N=<100) 9nt 160 197 N N 186 163 263 232 284
Hemoglobin g/dl 13.6 15.5 14.2 14.4 13.4 14.0 18.6 17.3 16.3 12.8
Hematocrit 0.40 0.45 0.44 0.44 0.40 0.41 0.63 0.52 0.53 0.60
Erythrocytes x1012/L 4.5 5.3 4.7 4.8 4.6 4.9 6.3 6.1 7.4 6.7
EEC + + + nt. nt. +. + + + +
Red cell mass N N N N nt. nt. ↑ ↑ ↑ ↑
Spleen, echogram cm . 13 16 13 16.5 11.8 13.7 13 14.3 16
Clinical diagnosisNo use of BM ET ET ET ET ET ET PV PV PV PV
Table 7A: Clinical features of 6 ET, and 4 patients carrying the JAK2V617F mutation
Case 1 2 3 4 5 6 7 8 9 10
Cellularity 60% 65% 90% 75% 80% 75% 80% 65% 80% 80%
M:E ratio 1 1 1 0,5 4 0,7 0,7 1 1.5 -
Myeloid lineage N N ↑ N ↑ N N N ↑ ↑
Erythroid lineage ↑ ↑ ↑ ↑ N ↑ ↑ ↑ ↑ ↑
Myelofibrosis: MF MF-0 MF-1 MF-0 MF-0 MF-0 MF-0 MF-0 MF-0 MF-1 MF-0
Diagnosis 2008 WHO ET ET ET ET MPNuc ET PV PV PV PV
Bone marrow diagn ET ET PV PV EMGM PV PV PV PV PV
Diagnosis2008 ECMP ET1 ET1 Pro-PV Pro-PV EMGM Pro-PV PV PV PV PV
Follow-up up to 2008 4 yrs 12 yrs 10 yrs 11 yrs 15 yrs 8 yrs 4 yrs 1 yrs 5 yrs 1 yrs
Treatment 2008 aspirin aspirin Low IFN HU no High IFN Phleb Phleb Phleb/HU Phleb/HU
Diagnosis in 2012 ET ET Remission PV EMGM PV PV PV PV PV
Treatment 2015 aspirin aspirin Very low IFN HU no Pheb Phleb Phleb HU HU
Table 7B: Bone marrow features of 10 JAK2V617F mutated thrombocythemia patients with the clinical diagnosis of ET in 6 and PV in 4 cases
  1971 1978 1985 1988 1989 1989a
Erythromelalgia - - + + + -
Peripheral blood            
Hemoglobin mmol/l 9.8 8.0 7.1 5.9 5.7 5.8
Platelets X109/l 285 265 421 484 811 223
LeukocytesX109/l 6.9 10.8 21.4 21.9 24 18
Bone Marrow            
Cellularity N ↑ ↑   ↑  
Erythropoiesis N N N   N  
Ringed sideroblasts - - -   -  
Megakaryocytes ↑ ↑ ↑↑   ↑↑  
Reticulum ↑ ↑↑ ↑↑↑   ↑↑↑  
Collagen - - ↑   ↑↑  
Osteoid - - -   +  
Myelodysplasia - - -   -  
Karyotype of bone marrow cells            
Spleen size on scan            
Length diameter cm   18   23    
*N, normal ; ↓,decreased; ↑, increased; -, absent; +, present. One arrow slight, two arrows pronounced, and three exceptional. The peripheral blood and bone marrow findings are consistent with agnogenic myeloid metaplasia in case 1.a While on treatment with Hydroxyurea
Source Michiels and Ten Kate, Amer J Hematol 1992; 39: 131-136 [17]
Table 8: Hematological Findings in Cases of Erythromelalgia and Atypical Thrombocythemia*