CBC: Difference between revisions
Ostermayer (talk | contribs) (Created page with "==Background== *The complete blood count (CBC) is one of the most commonly ordered laboratory tests in the emergency department<ref name="may">May JE, Marques MB, Reddy VVB, Gangaraju R. Three neglected numbers in the CBC: the RDW, MPV, and NRBC count. ''Cleve Clin J Med''. 2019;86(3):167-172. PMID 30849034.</ref> *Provides quantitative and qualitative information about three major cell lines: red blood cells (RBCs), white blood cells (WBCs), and platelets<ref name="long...") |
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*Performed by automated hematology analyzers; approximately 10–25% of samples require manual peripheral blood smear review to confirm abnormalities | *Performed by automated hematology analyzers; approximately 10–25% of samples require manual peripheral blood smear review to confirm abnormalities | ||
*Collected in an EDTA (purple/lavender top) tube | *Collected in an EDTA (purple/lavender top) tube | ||
* | *CBC typically refers to the basic count (WBC, RBC, hemoglobin, hematocrit, platelet count, RBC indices) | ||
* | *CBC with differential additionally provides the WBC differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils) and may report immature cells (bands, metamyelocytes, blasts) | ||
*Turn-around time in most EDs is 30–60 minutes from central lab; point-of-care CBC devices can provide results in < 5 minutes | *Turn-around time in most EDs is 30–60 minutes from central lab; point-of-care CBC devices can provide results in < 5 minutes | ||
| Line 67: | Line 67: | ||
*Fatigue, weakness, exertional dyspnea, pallor, tachycardia, dizziness/syncope | *Fatigue, weakness, exertional dyspnea, pallor, tachycardia, dizziness/syncope | ||
*Chest pain (demand ischemia in severe anemia) | *Chest pain (demand ischemia in severe anemia) | ||
* | *Microcytic (MCV < 80): iron deficiency (most common), thalassemia, anemia of chronic disease, sideroblastic anemia, lead poisoning | ||
* | *Normocytic (MCV 80–100): acute blood loss, anemia of chronic disease, hemolysis, renal failure, bone marrow failure | ||
* | *Macrocytic (MCV > 100): B12 deficiency, folate deficiency, alcoholism/liver disease, hypothyroidism, myelodysplastic syndrome, medications (e.g. methotrexate, hydroxyurea, antiretrovirals) | ||
===Leukocytosis (Elevated WBC)=== | ===Leukocytosis (Elevated WBC)=== | ||
| Line 79: | Line 79: | ||
*ANC < 1,500/μL = neutropenia; ANC < 500/μL = severe neutropenia | *ANC < 1,500/μL = neutropenia; ANC < 500/μL = severe neutropenia | ||
*Susceptibility to overwhelming bacterial and fungal infections | *Susceptibility to overwhelming bacterial and fungal infections | ||
*[[ | *[[Neutropenic fever]] (ANC < 500 + fever ≥ 38.3°C or ≥ 38.0°C sustained for 1 hour) is an oncologic emergency | ||
===Thrombocytopenia (Low Platelets)=== | ===Thrombocytopenia (Low Platelets)=== | ||
| Line 94: | Line 94: | ||
==Differential Diagnosis== | ==Differential Diagnosis== | ||
===Spurious / Falsely Abnormal Results=== | ===Spurious / Falsely Abnormal Results=== | ||
* | *Pseudothrombocytopenia: platelet clumping in EDTA tubes → falsely low platelet count; confirm by re-drawing in citrate (blue top) tube and examining peripheral smear | ||
* | *Hemolyzed specimen: falsely elevated potassium, LDH; can affect Hgb measurement | ||
* | *Lipemia: severely elevated triglycerides (> 2,000 mg/dL) can cause falsely elevated Hgb, MCHC, and MCH | ||
* | *Cold agglutinins: can cause falsely elevated MCV and falsely decreased RBC count | ||
* | *Leukocytosis with high WBC count (> 100,000/μL): may interfere with Hgb measurement | ||
* | *Hemodilution: IV fluids drawn proximal to the infusion site → falsely low counts | ||
==Evaluation== | ==Evaluation== | ||
| Line 112: | Line 112: | ||
*Suspected hematologic malignancy | *Suspected hematologic malignancy | ||
*Monitoring patients on chemotherapy or bone marrow–suppressing medications | *Monitoring patients on chemotherapy or bone marrow–suppressing medications | ||
*[[ | *[[Neutropenic fever]] screening in oncology patients | ||
*Abdominal pain (though utility is limited as a standalone test) | *Abdominal pain (though utility is limited as a standalone test) | ||
===Companion Studies Frequently Ordered with CBC=== | ===Companion Studies Frequently Ordered with CBC=== | ||
* | *Peripheral blood smear: morphologic evaluation (schistocytes in TTP/HUS/DIC, sickle cells, spherocytes, blasts) | ||
* | *Reticulocyte count: distinguish hyperproliferative vs. hypoproliferative anemia | ||
* | *[[Coagulation Studies]] (PT/INR, PTT): suspected coagulopathy or DIC | ||
* | *Type and screen / crossmatch: anticipated transfusion | ||
* | *Iron studies, B12, folate: workup of anemia | ||
* | *Haptoglobin, LDH, bilirubin, direct Coombs: suspected hemolytic anemia | ||
* | *[[BMP]] or [[CMP]]: electrolytes, renal function | ||
==Management== | ==Management== | ||
| Line 128: | Line 128: | ||
===Anemia=== | ===Anemia=== | ||
* | *Transfusion thresholds: | ||
**Hemoglobin < 7 g/dL: transfuse in most stable patients (restrictive strategy)<ref name="carson">Carson JL, Stanworth SJ, Dennis JA, et al. Transfusion thresholds for guiding red blood cell transfusion. ''Cochrane Database Syst Rev''. 2021;12(12):CD002042. PMID 34932836.</ref> | **Hemoglobin < 7 g/dL: transfuse in most stable patients (restrictive strategy)<ref name="carson">Carson JL, Stanworth SJ, Dennis JA, et al. Transfusion thresholds for guiding red blood cell transfusion. ''Cochrane Database Syst Rev''. 2021;12(12):CD002042. PMID 34932836.</ref> | ||
**Hemoglobin < 8 g/dL: consider transfusion in patients with cardiovascular disease | **Hemoglobin < 8 g/dL: consider transfusion in patients with cardiovascular disease | ||
| Line 138: | Line 138: | ||
*Identify and treat source of infection | *Identify and treat source of infection | ||
*Concern for [[Leukostasis|leukostasis]] if WBC > 100,000/μL (especially in AML): emergent hematology consultation, consider leukapheresis | *Concern for [[Leukostasis|leukostasis]] if WBC > 100,000/μL (especially in AML): emergent hematology consultation, consider leukapheresis | ||
* | *Left shift (bandemia > 10%) in the context of clinical illness supports bacterial infection and may prompt earlier antibiotic administration | ||
===Neutropenia / Febrile Neutropenia=== | ===Neutropenia / Febrile Neutropenia=== | ||
*[[ | *[[Neutropenic fever]] is a medical emergency | ||
*Empiric broad-spectrum antibiotics within 60 minutes of presentation (e.g. cefepime, piperacillin-tazobactam, or meropenem) | *Empiric broad-spectrum antibiotics within 60 minutes of presentation (e.g. cefepime, piperacillin-tazobactam, or meropenem) | ||
*Blood cultures before antibiotics if feasible, but do not delay treatment | *Blood cultures before antibiotics if feasible, but do not delay treatment | ||
| Line 160: | Line 160: | ||
==Emerging Applications== | ==Emerging Applications== | ||
* | *Red cell distribution width (RDW): Increasingly recognized as an independent prognostic marker in sepsis, heart failure, cardiac arrest, trauma, PE, and critical illness<ref name="yousefi"/><ref name="bazick">Bazick HS, Chang D, Mahadevappa K, Gibbons FK, Christopher KB. Red cell distribution width and all-cause mortality in critically ill patients. ''Crit Care Med''. 2011;39(8):1913-1921. PMID 21532476.</ref> | ||
**Elevated RDW (> 14.5%) is associated with increased 28-day and 30-day mortality across multiple disease states | **Elevated RDW (> 14.5%) is associated with increased 28-day and 30-day mortality across multiple disease states | ||
**Serial RDW measurement over 72 hours after admission may improve prognostication in sepsis<ref name="kim">Kim CH, Park JT, Kim EJ, et al. An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. ''Crit Care''. 2013;17(6):R282. PMID 24321201.</ref> | **Serial RDW measurement over 72 hours after admission may improve prognostication in sepsis<ref name="kim">Kim CH, Park JT, Kim EJ, et al. An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. ''Crit Care''. 2013;17(6):R282. PMID 24321201.</ref> | ||
* | *Neutrophil-to-lymphocyte ratio (NLR): Calculated from the differential; elevated NLR (> 6–10) is associated with worse outcomes in sepsis, ACS, PE, and various malignancies<ref name="zahorec">Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. ''Bratisl Lek Listy''. 2021;122(7):474-488. PMID 34161115.</ref> | ||
* | *Monocyte distribution width (MDW): A novel CBC-derived parameter available on some automated analyzers; FDA-cleared as an early sepsis screening biomarker in the ED<ref name="crouser">Crouser ED, Parrillo JE, Seymour CW, et al. Monocyte distribution width: a novel indicator of sepsis-2 and sepsis-3 in high-acuity patients. ''Crit Care Med''. 2019;47(8):1018-1025. PMID 31107279.</ref> | ||
==Disposition== | ==Disposition== | ||
*Disposition is driven by the underlying diagnosis, not the CBC result in isolation | *Disposition is driven by the underlying diagnosis, not the CBC result in isolation | ||
* | *Consider admission for: | ||
**Symptomatic anemia requiring transfusion or unstable hemoglobin | **Symptomatic anemia requiring transfusion or unstable hemoglobin | ||
**Febrile neutropenia (ANC < 500) | **Febrile neutropenia (ANC < 500) | ||
| Line 175: | Line 175: | ||
**Suspected hematologic malignancy (blasts on differential) | **Suspected hematologic malignancy (blasts on differential) | ||
**WBC > 100,000/μL with concern for leukostasis | **WBC > 100,000/μL with concern for leukostasis | ||
* | *Discharge with follow-up may be appropriate for: | ||
**Mild, chronic, asymptomatic anemia with known etiology and stable hemoglobin | **Mild, chronic, asymptomatic anemia with known etiology and stable hemoglobin | ||
**Mild thrombocytopenia (> 100,000/μL) without bleeding | **Mild thrombocytopenia (> 100,000/μL) without bleeding | ||
| Line 183: | Line 183: | ||
==See Also== | ==See Also== | ||
*[[Anemia]] | *[[Anemia]] | ||
*[[ | *[[Neutropenic fever]] | ||
*[[Leukocytosis]] | *[[Leukocytosis]] | ||
*[[Thrombocytopenia]] | *[[Thrombocytopenia]] | ||
*[[Thrombotic | *[[Thrombotic thrombocytopenic purpura]] | ||
*[[ | *[[DIC]] | ||
*[[Leukemia]] | *[[Leukemia]] | ||
*[[Transfusion Reactions]] | *[[Transfusion Reactions]] | ||
Latest revision as of 16:15, 19 March 2026
Background
- The complete blood count (CBC) is one of the most commonly ordered laboratory tests in the emergency department[1]
- Provides quantitative and qualitative information about three major cell lines: red blood cells (RBCs), white blood cells (WBCs), and platelets[2]
- Performed by automated hematology analyzers; approximately 10–25% of samples require manual peripheral blood smear review to confirm abnormalities
- Collected in an EDTA (purple/lavender top) tube
- CBC typically refers to the basic count (WBC, RBC, hemoglobin, hematocrit, platelet count, RBC indices)
- CBC with differential additionally provides the WBC differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils) and may report immature cells (bands, metamyelocytes, blasts)
- Turn-around time in most EDs is 30–60 minutes from central lab; point-of-care CBC devices can provide results in < 5 minutes
Components
Red Blood Cell Parameters
| Parameter | Normal Range (Adult) | Description |
|---|---|---|
| RBC count | M: 4.5–5.5 × 106/μL; F: 4.0–5.0 × 106/μL | Total number of red blood cells per volume |
| Hemoglobin (Hgb) | M: 13.5–17.5 g/dL; F: 12.0–16.0 g/dL | Oxygen-carrying protein in RBCs; most reliable indicator of anemia |
| Hematocrit (Hct) | M: 38.3–48.6%; F: 35.5–44.9% | Percentage of blood volume occupied by RBCs |
| MCV | 80–100 fL | Mean corpuscular volume; average RBC size; classifies anemia as microcytic (< 80), normocytic (80–100), or macrocytic (> 100) |
| MCH | 27–33 pg | Mean corpuscular hemoglobin; average hemoglobin mass per RBC |
| MCHC | 32–36 g/dL | Mean corpuscular hemoglobin concentration; average hemoglobin concentration per RBC |
| RDW | 11.5–14.5% | Red cell distribution width; measure of variation in RBC size (anisocytosis); elevated in iron deficiency, B12/folate deficiency, mixed anemias[3] |
| Reticulocyte count | 0.5–2.5% | Immature RBCs; must be specifically ordered; helps classify anemia as hypo- vs. hyperproliferative |
White Blood Cell Parameters
| Parameter | Normal Range (Adult) | Description |
|---|---|---|
| WBC count | 4,500–11,000/μL | Total white blood cell count |
| Neutrophils | 40–70% (1,800–7,700/μL) | Primary defense against bacterial infections; elevated (neutrophilia) in bacterial infection, stress, steroids, inflammation; decreased (neutropenia) in bone marrow failure, chemotherapy, drug reactions |
| Lymphocytes | 20–40% (1,000–4,800/μL) | Elevated in viral infections, CLL; decreased in HIV, immunosuppression, steroids |
| Monocytes | 2–8% (200–800/μL) | Elevated in chronic infections (TB, endocarditis), autoimmune disease, malignancy |
| Eosinophils | 1–4% (100–400/μL) | Elevated in allergic conditions, parasitic infections, drug reactions, adrenal insufficiency |
| Basophils | 0.5–1% (< 100/μL) | Elevated in myeloproliferative disorders (especially CML), allergic reactions |
| Bands (immature neutrophils) | 0–5% | Elevated ("bandemia" or "left shift") suggests acute bacterial infection or severe physiologic stress |
Platelet Parameters
| Parameter | Normal Range (Adult) | Description |
|---|---|---|
| Platelet count | 150,000–400,000/μL | Low: risk of spontaneous bleeding (< 50,000 increases surgical risk; < 10,000–20,000 risk of spontaneous hemorrhage); High: thrombocytosis — reactive vs. clonal |
| MPV | 7.5–12.0 fL | Mean platelet volume; larger platelets are younger and more metabolically active; elevated MPV with low platelets suggests peripheral destruction (e.g. ITP); low MPV with low platelets suggests bone marrow failure[1] |
Clinical Features
The CBC itself is a laboratory test, not a clinical condition. However, abnormalities in the CBC are associated with the following clinical presentations:
Anemia (Low Hgb/Hct)
- Fatigue, weakness, exertional dyspnea, pallor, tachycardia, dizziness/syncope
- Chest pain (demand ischemia in severe anemia)
- Microcytic (MCV < 80): iron deficiency (most common), thalassemia, anemia of chronic disease, sideroblastic anemia, lead poisoning
- Normocytic (MCV 80–100): acute blood loss, anemia of chronic disease, hemolysis, renal failure, bone marrow failure
- Macrocytic (MCV > 100): B12 deficiency, folate deficiency, alcoholism/liver disease, hypothyroidism, myelodysplastic syndrome, medications (e.g. methotrexate, hydroxyurea, antiretrovirals)
Leukocytosis (Elevated WBC)
- Fever, signs of infection, localized inflammation
- Significant leukocytosis (> 25,000–30,000/μL) should raise concern for serious bacterial infection, leukemoid reaction, or hematologic malignancy
- Leukocytosis with blasts on differential warrants emergent hematology consultation for suspected leukemia
Leukopenia / Neutropenia (Low WBC)
- ANC < 1,500/μL = neutropenia; ANC < 500/μL = severe neutropenia
- Susceptibility to overwhelming bacterial and fungal infections
- Neutropenic fever (ANC < 500 + fever ≥ 38.3°C or ≥ 38.0°C sustained for 1 hour) is an oncologic emergency
Thrombocytopenia (Low Platelets)
- Petechiae, purpura, mucosal bleeding, easy bruising
- Etiologies include: ITP, TTP, HIT, DIC, liver disease, medications, bone marrow failure, splenic sequestration
Thrombocytosis (Elevated Platelets)
- Reactive (infection, inflammation, iron deficiency, splenectomy, malignancy) vs. clonal (myeloproliferative neoplasms)
- Reactive thrombocytosis rarely causes thrombotic complications
Pancytopenia
- Reduction in all three cell lines; consider aplastic anemia, myelodysplasia, bone marrow infiltration (leukemia, lymphoma, myelofibrosis), severe megaloblastic anemia, overwhelming sepsis
Differential Diagnosis
Spurious / Falsely Abnormal Results
- Pseudothrombocytopenia: platelet clumping in EDTA tubes → falsely low platelet count; confirm by re-drawing in citrate (blue top) tube and examining peripheral smear
- Hemolyzed specimen: falsely elevated potassium, LDH; can affect Hgb measurement
- Lipemia: severely elevated triglycerides (> 2,000 mg/dL) can cause falsely elevated Hgb, MCHC, and MCH
- Cold agglutinins: can cause falsely elevated MCV and falsely decreased RBC count
- Leukocytosis with high WBC count (> 100,000/μL): may interfere with Hgb measurement
- Hemodilution: IV fluids drawn proximal to the infusion site → falsely low counts
Evaluation
ED Indications for Ordering a CBC
- Suspected infection or sepsis
- Hemorrhage, trauma, or suspected blood loss
- Suspected anemia (pallor, tachycardia, fatigue, syncope)
- Unexplained fever
- Petechiae, purpura, or abnormal bleeding
- Pre-operative evaluation
- Altered mental status
- Suspected hematologic malignancy
- Monitoring patients on chemotherapy or bone marrow–suppressing medications
- Neutropenic fever screening in oncology patients
- Abdominal pain (though utility is limited as a standalone test)
Companion Studies Frequently Ordered with CBC
- Peripheral blood smear: morphologic evaluation (schistocytes in TTP/HUS/DIC, sickle cells, spherocytes, blasts)
- Reticulocyte count: distinguish hyperproliferative vs. hypoproliferative anemia
- Coagulation Studies (PT/INR, PTT): suspected coagulopathy or DIC
- Type and screen / crossmatch: anticipated transfusion
- Iron studies, B12, folate: workup of anemia
- Haptoglobin, LDH, bilirubin, direct Coombs: suspected hemolytic anemia
- BMP or CMP: electrolytes, renal function
Management
Management is directed at the underlying cause identified by CBC abnormalities:
Anemia
- Transfusion thresholds:
- Hemoglobin < 7 g/dL: transfuse in most stable patients (restrictive strategy)[4]
- Hemoglobin < 8 g/dL: consider transfusion in patients with cardiovascular disease
- Active hemorrhage: transfuse irrespective of Hgb level; activate massive transfusion protocol if indicated
- Each unit of pRBCs should raise Hgb by approximately 1 g/dL
- Identify and treat underlying cause (GI bleed, menorrhagia, hemolysis, nutritional deficiency, etc.)
Leukocytosis
- Identify and treat source of infection
- Concern for leukostasis if WBC > 100,000/μL (especially in AML): emergent hematology consultation, consider leukapheresis
- Left shift (bandemia > 10%) in the context of clinical illness supports bacterial infection and may prompt earlier antibiotic administration
Neutropenia / Febrile Neutropenia
- Neutropenic fever is a medical emergency
- Empiric broad-spectrum antibiotics within 60 minutes of presentation (e.g. cefepime, piperacillin-tazobactam, or meropenem)
- Blood cultures before antibiotics if feasible, but do not delay treatment
Thrombocytopenia
- Platelet transfusion thresholds:
- < 10,000/μL: transfuse prophylactically (unless contraindicated, e.g. TTP, HIT)
- < 50,000/μL: transfuse if actively bleeding or pre-procedure
- < 100,000/μL: transfuse for CNS or ocular bleeding/procedures
- Do NOT transfuse platelets in suspected TTP or HIT — may worsen condition
- Examine peripheral smear for schistocytes if TTP/HUS suspected
Pancytopenia
- Hematology consultation
- Transfuse as needed for symptomatic anemia or bleeding
- Broad-spectrum antibiotics if febrile and neutropenic
- Avoid IM injections and rectal examinations in thrombocytopenic patients
Emerging Applications
- Red cell distribution width (RDW): Increasingly recognized as an independent prognostic marker in sepsis, heart failure, cardiac arrest, trauma, PE, and critical illness[3][5]
- Elevated RDW (> 14.5%) is associated with increased 28-day and 30-day mortality across multiple disease states
- Serial RDW measurement over 72 hours after admission may improve prognostication in sepsis[6]
- Neutrophil-to-lymphocyte ratio (NLR): Calculated from the differential; elevated NLR (> 6–10) is associated with worse outcomes in sepsis, ACS, PE, and various malignancies[7]
- Monocyte distribution width (MDW): A novel CBC-derived parameter available on some automated analyzers; FDA-cleared as an early sepsis screening biomarker in the ED[8]
Disposition
- Disposition is driven by the underlying diagnosis, not the CBC result in isolation
- Consider admission for:
- Symptomatic anemia requiring transfusion or unstable hemoglobin
- Febrile neutropenia (ANC < 500)
- New thrombocytopenia < 50,000/μL, especially with bleeding
- New pancytopenia
- Suspected hematologic malignancy (blasts on differential)
- WBC > 100,000/μL with concern for leukostasis
- Discharge with follow-up may be appropriate for:
- Mild, chronic, asymptomatic anemia with known etiology and stable hemoglobin
- Mild thrombocytopenia (> 100,000/μL) without bleeding
- Reactive leukocytosis with identified and treated source (e.g. minor infection)
- Ensure repeat CBC and appropriate follow-up for any new abnormality detected incidentally
See Also
- Anemia
- Neutropenic fever
- Leukocytosis
- Thrombocytopenia
- Thrombotic thrombocytopenic purpura
- DIC
- Leukemia
- Transfusion Reactions
- Coagulation Studies
- Peripheral Blood Smear
- Pancytopenia
External Links
- Three neglected numbers in the CBC: RDW, MPV, and NRBC count - Cleve Clin J Med 2019
- Transfusion thresholds for guiding red blood cell transfusion - Cochrane Database Syst Rev 2021
- Monocyte distribution width: a novel indicator of sepsis - Crit Care Med 2019
- RDW increase from baseline predicts mortality in severe sepsis - Crit Care 2013
- The value of a CBC for sepsis diagnosis and prognosis - Diagnostics 2021
References
- ↑ 1.0 1.1 May JE, Marques MB, Reddy VVB, Gangaraju R. Three neglected numbers in the CBC: the RDW, MPV, and NRBC count. Cleve Clin J Med. 2019;86(3):167-172. PMID 30849034.
- ↑ George-Gay B, Parker K. Understanding the complete blood count with differential. J Perianesth Nurs. 2003;18(2):96-117. PMID 12710004.
- ↑ 3.0 3.1 Yousefi B, Sanaie S, Ghamari AA, et al. Red cell distribution width as a novel prognostic marker in multiple clinical studies. Indian J Crit Care Med. 2020;24(1):49-54. PMID 32148347.
- ↑ Carson JL, Stanworth SJ, Dennis JA, et al. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021;12(12):CD002042. PMID 34932836.
- ↑ Bazick HS, Chang D, Mahadevappa K, Gibbons FK, Christopher KB. Red cell distribution width and all-cause mortality in critically ill patients. Crit Care Med. 2011;39(8):1913-1921. PMID 21532476.
- ↑ Kim CH, Park JT, Kim EJ, et al. An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. Crit Care. 2013;17(6):R282. PMID 24321201.
- ↑ Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy. 2021;122(7):474-488. PMID 34161115.
- ↑ Crouser ED, Parrillo JE, Seymour CW, et al. Monocyte distribution width: a novel indicator of sepsis-2 and sepsis-3 in high-acuity patients. Crit Care Med. 2019;47(8):1018-1025. PMID 31107279.