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Approach to Thrombocytopenia
Presentedby
Dr. Md SazzadZayedChowdhury
MD (Haematology)
DEFINITIONS
• Thrombocytopenia is defined as a platelet count below the lower
limit of normal.
Mild
• 100,000 to 150,000/microL
Moder
ate
• 50,000 to 99,000/microL
Severe
• <50,000/microL
Pitfalls
• Approximately 2.5 percent populations may have platelet count less
than 150,000/microL
• An individual may present with a significant decrease in platelet
count though still be within the 'normal' range (eg, a drop in platelet
count from 400,000 to 200,000/microL is concerning, even though
the value is still ≥150,000/microL). Such a reduction may be clinically
significant and requires evaluation. At a minimum, the platelet count
should be repeated.
• These issues also highlights the importance of obtaining previous
platelet counts (if available) to determine whether the count is stable
or trending downward.
When to worry about bleeding
• The concept of a "safe" platelet count is imprecise, lacks
evidence-based recommendations, and depends on the disorder
and on the patient (even with the same disorder).
• Severe spontaneous bleeding is rare; it is most likely with
platelet counts <20,000/microL, especially <10,000/microL.
When to worry about bleeding
- Clinical predictors of bleeding includes
 Prior bleeding episodes
 Presence of wet purpura and
 Haematuria.
When to worry about bleeding
• It is also important to consider other factors that may affect bleeding
risk (eg, platelet function defects, coagulation abnormalities).
• Patients with severe liver disease or disseminated intravascular
coagulation may have a greater risk of bleeding from coagulation
defects than from the thrombocytopenia.
When to worry about thrombosis
Patients with thrombocytopenia are at risk for thrombosis rather than,
or in addition to, bleeding. Though rare, it is important to consider
them because urgent treatment may be needed to prevent life-
threatening thrombotic events.
1. Heparin-induced thrombocytopenia
2. Vaccine-induced immune thrombotic thrombocytopenia (VITT)
3. Antiphospholipid syndrome
4. Disseminated intravascular coagulation
5. Thrombotic microangiopathy
PATHOPHYSIOLOGY OF THROMBOCYTOPENIA
Thrombocytopenia with neurological
symptom and high LDH
MS S N
37 F
Presented with occipital headache, slurring of speech (flactuating), on and off left
sided paraesthesia, LBP
Bruise in arm and shin
New onset thrombocytopenia (30) with anaemia (9.9)
CT brain Normal
Dugue and malaria Negative
DCT negative
LDH 820
INR 1.22, APTT 48, LA-negative, ANA- negative
Which single most investigation is important
for diagnosis
A. BMAT
B. PBF
C. MRI of Brain with MRA
D. ADAMTS13
E. Renal profile
Thrombocytopenia with anaemia
Mr M S N
27 M
PMH nil
Drug nil
Presentation was generalized weakness and LBP
new onset Severe Thrombocytopenia(68) with anaemia (7.5)
No bleeding/purpura
No organomegaly or lymphadenopathy
What should be the next plan?
A. BMAT
B. PBF
C. Haematology referral
D. Send iron and vitamin B12 study
E. Send DCT, LDH
Thrombocytopenia with leukopenia
Mr J B K
47 M
Nil PMH
COVID vaccination on 01/07/21 moderna
Presented with palpitation and tremor to AE on 10/07/21
Ref for new onset moderate thrombocytopenia (51) with leukopenia(3.1)
CRP 0.052 Lactate 1.1
Dengue and Malaria negative
PBF Bicytopenia (non diagnostic film)
What are the appropriate action for this
patient?
A. Looks for findings of thrombosis
B. Watch and wait for severe thrombocytopenia
C. Send anti PF4 antibody
D. Platelet transfusion
E. IV immunoglobulin
Thrombocytopenia, anaemia and obesity
39 M
PMH- DM, HTN,HLP, Asthma, Morbid Obesity 154kg
Exertional dyspnea, lethargy, occ epistaxis and gum bleeding
Chronic moderate thrombocytopenia for 3 years and anaemia
INR 1.50
Albumin 27 g/l
Hep B and C negative
Q: what's the likely diagnosis
A. ITP
B. Chronic liver disease
C. CML
D. DITP
Isolated thrombocytopenia
• Mr A R H
• 17 M
• Presented with purpura and oral mucosal bleeding-3 days
New onset isolated thrombocytopenia
• Hb 14, WCC 10.7 PLATELET 1
• DCT Negative, LDH 181
• ANA negative
• TFT and LFT- Normal
• Coagulation screen INR 1.1, APTT 30.9
• Viral/infection screen-Malaria Neg, Dengue Neg, CMV Neg, Hep B, C and HIV negative
• CRP 0.7
The obvious clinical diagnosis is?
Initial Mandatory Questions
● Is the thrombocytopenia real?
Not a laboratory error, can be done by repeating the CBC and reviewing the
peripheral blood smear
● Is the thrombocytopenia new?
A new reduction is more concerning than a stable because it suggests the
possibility of an evolving condition.
New- BM disorder, DIC, Drugs(Heparin, Vaccine)
Chronic- ITP, CLD, HIV, connective tissue disorder
● Are there other hematologic abnormalities?
Anemia, leukopenia, leukocytosis, coagulation abnormalities generally
suggest a more serious diagnosis than isolated thrombocytopenia
Targeted History
- History of bleeding (eg, petechiae, ecchymoses, epistaxis,
hematemesis, melena, heavy menstrual bleeding).
- Infectious exposures, including recent infections (viral, bacterial,
rickettsia), recent travel to an area endemic for malaria, dengue virus,
leptospirosis, rickettsia infections and viral hemorrhagic fevers.
- Medication exposures – It is important to include new prescriptions,
medications that are only taken intermittently, over-the-counter
medicines (eg, aspirin, nonsteroidal anti-inflammatory drugs), herbal
remedies, vaccines
Targeted History
- Other medical conditions, including hematologic disorders;
rheumatologic diseases; bariatric surgery or poor nutritional status;
blood product transfusion or organ transplantation
- Prior platelet counts
= Family history of bleeding disorders and/or thrombocytopenia.
Relevant findings
Specific diagnoses to consider depend on the other clinical findings. As
examples:
•Fever – Possible infection, sepsis, disseminated intravascular coagulation
(DIC)
•Hepatosplenomegaly – Possible liver disease with hypersplenism,
Leukaemia or lymphoma
•Neurologic findings – Possible TTP, HUS, DITMA, vitamin B12 deficiency
•Lymphadenopathy – Possible infection, lymphoma, other malignancy
•Thrombosis – Possible HIT, antiphospholipid syndrome (APS), or paroxysmal
nocturnal hemoglobinuria (PNH) or VITT
LABORATORY TESTING
Repeat CBC and when to do
• For symptomatic patients (eg, signs of bleeding) or those with severe
thrombocytopenia (ie, <50,000/microL), such retesting should be
performed immediately.
• For asymptomatic patients (eg, non-bleeding, no associated
comorbidities) with moderate thrombocytopenia (ie, 50,000 to
100,000/microL), testing may be repeated in one to two weeks,
provided the patient is advised to report immediately any changes in
clinical status or bleeding during this interval.
6 7 8
4 5
1 2 3 9
Thrombocytopenic emergencies requiring
immediate haematology referral
• Bleeding in the setting of severe thrombocytopenia
(ie, platelet count <50,000/microL)
• Suspected acute leukemia, aplastic anemia, or other
bone marrow failure syndrome
• Urgently needed invasive procedure with severe
thrombocytopenia
• Pregnancy with severe thrombocytopenia
Thrombocytopenic emergencies requiring
immediate haematology referral
• Suspected heparin-induced thrombocytopenia (HIT),
vaccine-induced immune thrombotic
thrombocytopenia (VITT), or post-transfusion purpura
• Suspected thrombotic thrombocytopenic purpura
(TTP), hemolytic uremic syndrome (HUS), or drug-
induced thrombotic microangiopathy (DITMA)
Thank you
Thrombocytopenia with neurological symptom and high LDH
37 F
Presented with fluctuating neurological symptoms
New onset thrombocytopenia(30) with anaemia(9.9)
CT brain Normal
Dengue and malaria Negative
DCT negative
INR 1.22, APTT 48, LA-negative, ANA- negative
LDH 820
DATE 21/12 22/12 23/12 24/12
PLEX
25/12 26/12 28/12 30/12 01/01 02/01
Platelet 30 23 18 23 35 49 74 77 112 232
LDH 820 963 528 262 241 405 180 280
R
Mr M S Z
24 M
Fever, headache, abdominal pain, vomiting and skin rash-4 days
New onset thrombocytopenia (5) and anaemia (Hb 5)
Treated with TPE 10 session and steroid
DATE 03/01 04/01 05/01 06/01 07/01 08/01 09/01 10/01 11/01
Platelet 6 5 9 39 78 117 154 168 180
LDH 2823 2005 1036 535 443 403 269 241 210
R
Thrombocytopenia with anaemia
Mr M S N
27 M
PMH nil
Drug nil
Presentation was generalized weakness and LBP
New onset Moderate thrombocytopenia (68) with anaemia (7.5)
No bleeding/purpura
No organomegaly or lymphadenopathy
R
Thrombocytopenia with fever
Mrs J S
41 F
Presented with Fever and suprapubic pain on 07/04/2022
Developed hypotension and started inotropes on 08/04/2022
INR 2.41 APTT 36
Lactate 7.3
CRP 2.2(7/4)>13.8(10/4)> 0.536(15/4)
Blood CS E Coli
16/05/202215/05/202213/04/202213/04/2022 11/4/2022 10/4/2022 9/4/2022 8/4/2022 7/4/2022
Series 1 281 277 109 61 36 22 41 114 208
281 277
109
61
36
22
41
114
208
Trends of platelet
CRP 13.8
CRP 0.53
CRP 2.2
R
Thrombocytopenia with fever
Mr H A L
38 M
K/C DM, HTN, HLP
Presented with Light headedness, giddiness and vomiting on 13/06/22
Recorded febrile(38.9) in AE
New onset mild thrombocytopenia (106) followed by downtrend upto
20
PBF thrombocytopenia with reactive lymphocyte
Deranged LFT
Dengue NS1 positive
R
Thrombocytopenia, anaemia and obesity
39 M
PHM DM, HTN, HLP, Asthma, Morbid Obesity 154kg
Exertional dyspnea, lethargy, occ epistaxis and gum bleeding
Chronic thrombocytopenia for 3 years and anaemia
INR 1.50
Albumin 27 g/l
Hep B and C negative
Date 17/04/2022
14/04/2022
12/04/2022 25/09/2019 08/04/2018 12/01/2017
Platelet 75 67 65 110 124 187
Hb 7.5 7.2 7.7 10.8 13.1 15.3
US abdomen: Cirrhotic liver with portal HTN
R
Thrombocytopenia with leukopenia
Mr J B K
47 M
Nil PMH
COVID vaccination on 01/07/21 (moderna)
Presented with palpitation and tremor to AE on 10/07/21
Ref for new onset moderate thrombocytopenia (51) with leukopenia(3.1)
CRP 0.052 Lactate 1.1
Dengue and Malaria negative
PBF Bicytopenia (non diagnostic film)
Trend of Platelet, MPV and WBC
Date WBC Platelet Mean Platelet
Volume
10/07/2021 3.1 51 9.7
11/07/2021 2.8 40 10.5
12/07/2021 3.4 57 11.6
14/07/2021 3.8 86 11.3
22/07/2021 6.0 456 9.7
R
Isolated thrombocytopenia
• Mr A R H
• 17 M
• Presented with rash and oral mucosal bleeding-3 days
New onset isolated thrombocytopenia
• Hb 14, WCC 10.7 PLATELET 1
• DCT Negative, LDH 181
• ANA negative
• TFT and LFT- Normal
• Coagulation screen INR 1.1, APTT 30.9
• Viral/infection screen-Malaria Neg, Dengue Neg, CMV Neg, Hep B, C and HIV negative
• CRP 0.7 IVIG
R
Megaloblastic anaemia related
thrombocytopenia
59 M
PMH- HTN, HLP
Presented with epigastric pain and loss of appetite
Macrocytic anaemia (5.9), leukopenia(2.0) and moderate
thrombocytopenia (69)
Vit B12 <109
Iron- 16.6
Anti-parietal cell antibody- positive
Date 01/06/22 04/06/22 13/06/22
Hb 5.8 8.1 10.4
Platelet 69 66 519
WBC 2.0 3.6 10.4
MCV 117 105 106
Retics (4.85)
R

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Approach_to_Thrombocytopenia.pptx

  • 1. Approach to Thrombocytopenia Presentedby Dr. Md SazzadZayedChowdhury MD (Haematology)
  • 2. DEFINITIONS • Thrombocytopenia is defined as a platelet count below the lower limit of normal. Mild • 100,000 to 150,000/microL Moder ate • 50,000 to 99,000/microL Severe • <50,000/microL
  • 3. Pitfalls • Approximately 2.5 percent populations may have platelet count less than 150,000/microL • An individual may present with a significant decrease in platelet count though still be within the 'normal' range (eg, a drop in platelet count from 400,000 to 200,000/microL is concerning, even though the value is still ≥150,000/microL). Such a reduction may be clinically significant and requires evaluation. At a minimum, the platelet count should be repeated. • These issues also highlights the importance of obtaining previous platelet counts (if available) to determine whether the count is stable or trending downward.
  • 4. When to worry about bleeding • The concept of a "safe" platelet count is imprecise, lacks evidence-based recommendations, and depends on the disorder and on the patient (even with the same disorder). • Severe spontaneous bleeding is rare; it is most likely with platelet counts <20,000/microL, especially <10,000/microL.
  • 5. When to worry about bleeding - Clinical predictors of bleeding includes  Prior bleeding episodes  Presence of wet purpura and  Haematuria.
  • 6. When to worry about bleeding • It is also important to consider other factors that may affect bleeding risk (eg, platelet function defects, coagulation abnormalities). • Patients with severe liver disease or disseminated intravascular coagulation may have a greater risk of bleeding from coagulation defects than from the thrombocytopenia.
  • 7. When to worry about thrombosis Patients with thrombocytopenia are at risk for thrombosis rather than, or in addition to, bleeding. Though rare, it is important to consider them because urgent treatment may be needed to prevent life- threatening thrombotic events. 1. Heparin-induced thrombocytopenia 2. Vaccine-induced immune thrombotic thrombocytopenia (VITT) 3. Antiphospholipid syndrome 4. Disseminated intravascular coagulation 5. Thrombotic microangiopathy
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  • 10. Thrombocytopenia with neurological symptom and high LDH MS S N 37 F Presented with occipital headache, slurring of speech (flactuating), on and off left sided paraesthesia, LBP Bruise in arm and shin New onset thrombocytopenia (30) with anaemia (9.9) CT brain Normal Dugue and malaria Negative DCT negative LDH 820 INR 1.22, APTT 48, LA-negative, ANA- negative
  • 11. Which single most investigation is important for diagnosis A. BMAT B. PBF C. MRI of Brain with MRA D. ADAMTS13 E. Renal profile
  • 12. Thrombocytopenia with anaemia Mr M S N 27 M PMH nil Drug nil Presentation was generalized weakness and LBP new onset Severe Thrombocytopenia(68) with anaemia (7.5) No bleeding/purpura No organomegaly or lymphadenopathy
  • 13. What should be the next plan? A. BMAT B. PBF C. Haematology referral D. Send iron and vitamin B12 study E. Send DCT, LDH
  • 14. Thrombocytopenia with leukopenia Mr J B K 47 M Nil PMH COVID vaccination on 01/07/21 moderna Presented with palpitation and tremor to AE on 10/07/21 Ref for new onset moderate thrombocytopenia (51) with leukopenia(3.1) CRP 0.052 Lactate 1.1 Dengue and Malaria negative PBF Bicytopenia (non diagnostic film)
  • 15. What are the appropriate action for this patient? A. Looks for findings of thrombosis B. Watch and wait for severe thrombocytopenia C. Send anti PF4 antibody D. Platelet transfusion E. IV immunoglobulin
  • 16. Thrombocytopenia, anaemia and obesity 39 M PMH- DM, HTN,HLP, Asthma, Morbid Obesity 154kg Exertional dyspnea, lethargy, occ epistaxis and gum bleeding Chronic moderate thrombocytopenia for 3 years and anaemia INR 1.50 Albumin 27 g/l Hep B and C negative
  • 17. Q: what's the likely diagnosis A. ITP B. Chronic liver disease C. CML D. DITP
  • 18. Isolated thrombocytopenia • Mr A R H • 17 M • Presented with purpura and oral mucosal bleeding-3 days New onset isolated thrombocytopenia • Hb 14, WCC 10.7 PLATELET 1 • DCT Negative, LDH 181 • ANA negative • TFT and LFT- Normal • Coagulation screen INR 1.1, APTT 30.9 • Viral/infection screen-Malaria Neg, Dengue Neg, CMV Neg, Hep B, C and HIV negative • CRP 0.7
  • 19. The obvious clinical diagnosis is?
  • 20. Initial Mandatory Questions ● Is the thrombocytopenia real? Not a laboratory error, can be done by repeating the CBC and reviewing the peripheral blood smear ● Is the thrombocytopenia new? A new reduction is more concerning than a stable because it suggests the possibility of an evolving condition. New- BM disorder, DIC, Drugs(Heparin, Vaccine) Chronic- ITP, CLD, HIV, connective tissue disorder ● Are there other hematologic abnormalities? Anemia, leukopenia, leukocytosis, coagulation abnormalities generally suggest a more serious diagnosis than isolated thrombocytopenia
  • 21. Targeted History - History of bleeding (eg, petechiae, ecchymoses, epistaxis, hematemesis, melena, heavy menstrual bleeding). - Infectious exposures, including recent infections (viral, bacterial, rickettsia), recent travel to an area endemic for malaria, dengue virus, leptospirosis, rickettsia infections and viral hemorrhagic fevers. - Medication exposures – It is important to include new prescriptions, medications that are only taken intermittently, over-the-counter medicines (eg, aspirin, nonsteroidal anti-inflammatory drugs), herbal remedies, vaccines
  • 22. Targeted History - Other medical conditions, including hematologic disorders; rheumatologic diseases; bariatric surgery or poor nutritional status; blood product transfusion or organ transplantation - Prior platelet counts = Family history of bleeding disorders and/or thrombocytopenia.
  • 23. Relevant findings Specific diagnoses to consider depend on the other clinical findings. As examples: •Fever – Possible infection, sepsis, disseminated intravascular coagulation (DIC) •Hepatosplenomegaly – Possible liver disease with hypersplenism, Leukaemia or lymphoma •Neurologic findings – Possible TTP, HUS, DITMA, vitamin B12 deficiency •Lymphadenopathy – Possible infection, lymphoma, other malignancy •Thrombosis – Possible HIT, antiphospholipid syndrome (APS), or paroxysmal nocturnal hemoglobinuria (PNH) or VITT
  • 24. LABORATORY TESTING Repeat CBC and when to do • For symptomatic patients (eg, signs of bleeding) or those with severe thrombocytopenia (ie, <50,000/microL), such retesting should be performed immediately. • For asymptomatic patients (eg, non-bleeding, no associated comorbidities) with moderate thrombocytopenia (ie, 50,000 to 100,000/microL), testing may be repeated in one to two weeks, provided the patient is advised to report immediately any changes in clinical status or bleeding during this interval.
  • 25. 6 7 8 4 5 1 2 3 9
  • 26. Thrombocytopenic emergencies requiring immediate haematology referral • Bleeding in the setting of severe thrombocytopenia (ie, platelet count <50,000/microL) • Suspected acute leukemia, aplastic anemia, or other bone marrow failure syndrome • Urgently needed invasive procedure with severe thrombocytopenia • Pregnancy with severe thrombocytopenia
  • 27. Thrombocytopenic emergencies requiring immediate haematology referral • Suspected heparin-induced thrombocytopenia (HIT), vaccine-induced immune thrombotic thrombocytopenia (VITT), or post-transfusion purpura • Suspected thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or drug- induced thrombotic microangiopathy (DITMA)
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  • 30. Thrombocytopenia with neurological symptom and high LDH 37 F Presented with fluctuating neurological symptoms New onset thrombocytopenia(30) with anaemia(9.9) CT brain Normal Dengue and malaria Negative DCT negative INR 1.22, APTT 48, LA-negative, ANA- negative LDH 820 DATE 21/12 22/12 23/12 24/12 PLEX 25/12 26/12 28/12 30/12 01/01 02/01 Platelet 30 23 18 23 35 49 74 77 112 232 LDH 820 963 528 262 241 405 180 280 R
  • 31. Mr M S Z 24 M Fever, headache, abdominal pain, vomiting and skin rash-4 days New onset thrombocytopenia (5) and anaemia (Hb 5) Treated with TPE 10 session and steroid DATE 03/01 04/01 05/01 06/01 07/01 08/01 09/01 10/01 11/01 Platelet 6 5 9 39 78 117 154 168 180 LDH 2823 2005 1036 535 443 403 269 241 210 R
  • 32. Thrombocytopenia with anaemia Mr M S N 27 M PMH nil Drug nil Presentation was generalized weakness and LBP New onset Moderate thrombocytopenia (68) with anaemia (7.5) No bleeding/purpura No organomegaly or lymphadenopathy R
  • 33. Thrombocytopenia with fever Mrs J S 41 F Presented with Fever and suprapubic pain on 07/04/2022 Developed hypotension and started inotropes on 08/04/2022 INR 2.41 APTT 36 Lactate 7.3 CRP 2.2(7/4)>13.8(10/4)> 0.536(15/4) Blood CS E Coli
  • 34. 16/05/202215/05/202213/04/202213/04/2022 11/4/2022 10/4/2022 9/4/2022 8/4/2022 7/4/2022 Series 1 281 277 109 61 36 22 41 114 208 281 277 109 61 36 22 41 114 208 Trends of platelet CRP 13.8 CRP 0.53 CRP 2.2 R
  • 35. Thrombocytopenia with fever Mr H A L 38 M K/C DM, HTN, HLP Presented with Light headedness, giddiness and vomiting on 13/06/22 Recorded febrile(38.9) in AE New onset mild thrombocytopenia (106) followed by downtrend upto 20 PBF thrombocytopenia with reactive lymphocyte Deranged LFT
  • 37. Thrombocytopenia, anaemia and obesity 39 M PHM DM, HTN, HLP, Asthma, Morbid Obesity 154kg Exertional dyspnea, lethargy, occ epistaxis and gum bleeding Chronic thrombocytopenia for 3 years and anaemia INR 1.50 Albumin 27 g/l Hep B and C negative
  • 38. Date 17/04/2022 14/04/2022 12/04/2022 25/09/2019 08/04/2018 12/01/2017 Platelet 75 67 65 110 124 187 Hb 7.5 7.2 7.7 10.8 13.1 15.3 US abdomen: Cirrhotic liver with portal HTN R
  • 39. Thrombocytopenia with leukopenia Mr J B K 47 M Nil PMH COVID vaccination on 01/07/21 (moderna) Presented with palpitation and tremor to AE on 10/07/21 Ref for new onset moderate thrombocytopenia (51) with leukopenia(3.1) CRP 0.052 Lactate 1.1 Dengue and Malaria negative PBF Bicytopenia (non diagnostic film)
  • 40. Trend of Platelet, MPV and WBC Date WBC Platelet Mean Platelet Volume 10/07/2021 3.1 51 9.7 11/07/2021 2.8 40 10.5 12/07/2021 3.4 57 11.6 14/07/2021 3.8 86 11.3 22/07/2021 6.0 456 9.7 R
  • 41. Isolated thrombocytopenia • Mr A R H • 17 M • Presented with rash and oral mucosal bleeding-3 days New onset isolated thrombocytopenia • Hb 14, WCC 10.7 PLATELET 1 • DCT Negative, LDH 181 • ANA negative • TFT and LFT- Normal • Coagulation screen INR 1.1, APTT 30.9 • Viral/infection screen-Malaria Neg, Dengue Neg, CMV Neg, Hep B, C and HIV negative • CRP 0.7 IVIG R
  • 42. Megaloblastic anaemia related thrombocytopenia 59 M PMH- HTN, HLP Presented with epigastric pain and loss of appetite Macrocytic anaemia (5.9), leukopenia(2.0) and moderate thrombocytopenia (69) Vit B12 <109 Iron- 16.6 Anti-parietal cell antibody- positive
  • 43. Date 01/06/22 04/06/22 13/06/22 Hb 5.8 8.1 10.4 Platelet 69 66 519 WBC 2.0 3.6 10.4 MCV 117 105 106 Retics (4.85) R