Introduction
Pancytopenia, a condition characterized by the simultaneous decrease in all three major blood cell lines – red blood cells, white blood cells, and platelets – is not a disease itself but rather a clinical signpost pointing towards a range of underlying health issues. For automotive technicians, understanding diagnostic processes is crucial for effectively troubleshooting complex vehicle problems. Similarly, in the realm of human health, diagnosing pancytopenia is an intricate puzzle that requires a systematic approach to uncover the root cause. This article provides a comprehensive guide to Pancytopenia Diagnosis, mirroring the meticulous diagnostic strategies employed in automotive repair, to aid healthcare professionals in navigating this challenging condition. Just as a mechanic methodically checks each system of a car to identify the source of a malfunction, diagnosing pancytopenia necessitates a thorough evaluation to pinpoint the etiology, which could stem from infections, autoimmune disorders, genetic factors, nutritional deficiencies, or malignancies. Accurate diagnosis is the cornerstone of effective treatment and predicting patient prognosis. Anyone exhibiting pancytopenia requires a detailed investigation to determine the underlying cause, and this guide will illuminate the most prevalent etiologies, delineate diagnostic pathways, and emphasize the vital role of a multidisciplinary healthcare team in patient care.
Etiology of Pancytopenia: Unraveling the Causes
Just as understanding the engine’s components is key to diagnosing car trouble, grasping the diverse etiologies of pancytopenia is fundamental to its diagnosis. The causes of pancytopenia can be broadly classified into two main categories, much like categorizing car problems as engine-related or transmission-related: central and peripheral. Central causes are related to decreased production of blood cells in the bone marrow, the body’s “factory” for blood cells, while peripheral causes involve increased destruction or removal of blood cells from circulation, akin to a car part wearing out prematurely.
Decreased Production (Central Type)
Reduced blood cell production, the central type of pancytopenia, is frequently linked to issues within the bone marrow itself. Nutritional deficiencies are a significant factor, comparable to a car engine malfunctioning due to poor fuel quality. Bone marrow failure, known as aplastic anemia, represents a severe form of central pancytopenia. Aplastic anemia can arise from idiopathic or autoimmune reactions, similar to unexplained electrical faults in a vehicle. It can also be triggered by infections, like parvovirus B19, hepatitis, HIV, cytomegalovirus (CMV), or Epstein-Barr virus (EBV), which can be likened to a computer virus disrupting a car’s electronic control unit. Certain medications and chemotherapeutic agents, such as methotrexate, dapsone, carbimazole, carbamazepine, and chloramphenicol, are also known culprits, acting like harmful additives that damage engine components. Inadequate nutrient intake, as seen in eating disorders and alcoholism, or malabsorption issues further contribute to decreased production, mirroring the effects of fuel line blockages on engine performance.
Bone Marrow Infiltration or Replacement
Similar to debris clogging a car’s air filter, bone marrow infiltration or replacement hinders blood cell production. This occurs when the bone marrow is invaded by malignant cells, as in lymphoma, leukemia, and multiple myeloma, or by granulomatous disorders. Metastatic tumors can also spread to the bone marrow, causing replacement and leading to pancytopenia in later stages of disease, akin to rust gradually weakening a car’s chassis.
Increased Destruction (Peripheral Type)
Peripheral destruction, the second major category, involves the accelerated breakdown of blood cells outside the bone marrow. Autoimmune conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) can lead to the body’s immune system attacking its own blood cells, much like a car’s alarm system malfunctioning and draining the battery. Splenic sequestration, often associated with alcoholic liver cirrhosis, HIV, tuberculosis, and malaria, results in the spleen, an organ that filters blood, trapping and destroying excessive numbers of blood cells. Hypersplenism particularly affects platelets and red blood cells more than white blood cells.
COVID-19 and Pancytopenia
The recent COVID-19 pandemic has highlighted another cause of pancytopenia. The SARS-CoV-2 virus has been reported to induce pancytopenia in some patients. Bone marrow aspiration in these cases has revealed viral infection and infiltration, suggesting a direct impact of the virus on blood cell production, similar to an external force damaging a car’s engine.
Idiopathic Cytopenias
Despite thorough investigation, some cases of cytopenia remain unexplained, classified as idiopathic cytopenias of unknown significance (ICUS). These are analogous to intermittent car problems that defy diagnosis even after extensive checks.
Mechanisms of Pancytopenia: Table 1
| Mechanism | Examples |
|---|---|
| Decreased Production | Nutritional deficiencies (B12, folate), Aplastic Anemia, Infections (Parvovirus B19, HIV, Hepatitis), Drugs |
| Bone Marrow Infiltration | Leukemia, Lymphoma, Metastatic Cancer, Granulomatous Diseases |
| Increased Destruction | Autoimmune Disorders (SLE, RA), Hypersplenism, Hemophagocytic Lymphohistiocytosis (HLH) |
Drugs Causing Pancytopenia: Table 2
| Drug Category | Examples |
|---|---|
| Antibiotics | Chloramphenicol, Linezolid |
| Anticonvulsants | Carbamazepine |
| Chemotherapy Agents | Methotrexate |
| Antithyroid Drugs | Carbimazole |
| Anti-inflammatory | Aspirin, Salicylates |
| Antiretrovirals | Zidovudine |
Understanding these diverse etiologies is the first step in the diagnostic process, much like familiarizing oneself with common car problems before attempting repairs.
Table 1: Mechanisms of Pancytopenia. This table summarizes the different mechanisms that can lead to pancytopenia, including decreased production, bone marrow infiltration, and increased destruction, providing examples for each category.
Table 2: Drugs Causing Pancytopenia. This table lists examples of drug categories and specific drugs known to potentially cause pancytopenia as a side effect.
Epidemiology of Pancytopenia: Prevalence and Patterns
Just as certain car models are more prone to specific issues, pancytopenia exhibits epidemiological patterns related to age, geography, and underlying causes. Pancytopenia incidence often shows a bimodal distribution, peaking in children and adults in their 3rd and 4th decades of life. Literature suggests a slight male predominance, with male to female ratios ranging from 1.4:1 to 2.6:1. Conditions like multiple myeloma and myelodysplastic syndrome are more commonly observed in older populations, whereas acute leukemia and parvovirus B19 infections are more prevalent in younger individuals.
Geographic and sociocultural factors significantly influence the predominant causes of pancytopenia, particularly megaloblastic anemia, which is often linked to nutritional deficiencies. Gender does not seem to play a significant role in megaloblastic anemia prevalence. Interestingly, higher rates of pancytopenia, especially due to infections and drug-induced causes, are observed in Eastern countries and developing nations compared to the West, possibly reflecting differences in healthcare access, environmental exposures, and medication usage patterns.
Studies across different regions reveal varying etiologies. In North America, myeloid neoplasms (acute myeloid leukemia, myelodysplasia, non-Hodgkin lymphoma, hairy cell leukemia, and precursor B acute lymphoblastic leukemia) are the most common causes, followed by aplastic anemia, megaloblastic anemia, and HIV infections. A 2013 study in India identified hypersplenism, infections, myelosuppression (cancer, chemotherapy, drug toxicity, or radiotherapy), and megaloblastic anemia as the most frequent causes. Earlier Indian research highlighted megaloblastic anemia as the leading cause, followed by aplastic anemia. In Mexico, myelodysplastic syndromes and megaloblastic anemia are most prevalent, succeeded by acute myeloblastic leukemia, acute lymphoblastic leukemia, hypersplenism, and aplastic anemia. Turkey’s data points to megaloblastic anemia as the primary cause, with acute myeloid leukemia and aplastic anemia following.
Understanding these epidemiological variations is akin to knowing the common car problems in different climates or regions, helping clinicians to anticipate likely causes based on patient demographics and geographic location.
Pathophysiology of Pancytopenia: Mechanisms at Play
Similar to understanding the mechanical principles behind a car malfunction, elucidating the pathophysiology of pancytopenia is crucial for effective diagnosis and treatment. The underlying pathophysiology is highly dependent on the specific cause of pancytopenia.
In aplastic anemia, the pathophysiology involves an autoimmune-mediated T-cell activation, which mistakenly targets and destroys hematopoietic stem cells, the precursors of blood cells in the bone marrow. This is analogous to an autoimmune reaction damaging critical engine parts. Bone marrow suppression can also be directly induced by cytotoxic effects of medications like methotrexate, anticonvulsants, and chemotherapeutic agents, acting like toxic substances poisoning the bone marrow. In myelodysplastic syndrome, ineffective hematopoiesis occurs within the bone marrow, meaning blood cell production is faulty and inefficient, akin to a factory producing defective car parts.
Sepsis, a severe systemic infection, leads to pancytopenia through a combination of mechanisms: marrow suppression, hypersplenism, and consumptive coagulopathy, which act synergistically. This is comparable to multiple system failures in a car caused by a single underlying issue. Viral infections induce pancytopenia through mechanisms that modulate hematopoietic stem cells, disrupting normal blood cell development. A massive cytokine storm, an overreaction of the immune system, has been implicated in SARS-CoV-2-related pancytopenia, representing an extreme immune response that damages the bone marrow. Paroxysmal nocturnal hemoglobinuria (PNH) is a genetic disorder characterized by the absence of glycophosphatidylinositol (GPI)-linked proteins, such as CD55 and CD59, which normally protect blood cells from complement-mediated destruction. This genetic defect results in the immune system destroying the patient’s own blood cells, similar to a manufacturing defect making car parts vulnerable to corrosion. PNH involves a mutation in phosphatidylinositol glycan class A (PIGA) proteins.
By understanding these diverse pathophysiological pathways, clinicians can better target their diagnostic investigations and tailor treatment strategies, much like a mechanic uses knowledge of engine mechanics to diagnose and repair car problems effectively.
History and Physical Examination in Pancytopenia Diagnosis
Just as a mechanic starts with a customer’s description of car problems and a visual inspection, the diagnostic process for pancytopenia begins with a detailed patient history and physical examination. The clinical presentation of pancytopenia can vary greatly, ranging from asymptomatic cases of mild pancytopenia to life-threatening emergencies in severe cases. Patients may present with symptoms reflecting deficiencies in any of the three blood cell lines.
Anemia, a deficiency in red blood cells, can manifest as shortness of breath, fatigue, and chest pain, similar to a car struggling to climb a hill due to low fuel or engine weakness. Leukopenia, a decrease in white blood cells (primarily neutrophils), increases susceptibility to infections. Thrombocytopenia, a platelet deficiency, results in bruising, petechiae (small red spots under the skin), and a tendency to bleed easily, much like a car with faulty brakes increasing the risk of accidents. Severe neutropenia can lead to serious infections. Underlying liver disease, which can contribute to pancytopenia, may present with anorexia, nausea, or lethargy. Splenic sequestration can cause left upper quadrant pain due to spleen enlargement. Constitutional symptoms, such as fever, weight loss, and night sweats, may indicate underlying autoimmune disorders or malignancies.
A thorough patient history is paramount. This should include inquiries about symptoms of autoimmune conditions, malignancies, recent infections, medication history (including over-the-counter drugs and supplements), chemotherapy or radiation therapy exposure. A detailed nutritional history is also crucial, as subtle malabsorption issues can present with pancytopenia as the primary manifestation. Family history should be explored to identify potential inherited conditions like Fanconi anemia.
Physical examination may reveal pallor (paleness), petechiae, ulcers, and rashes. Signs of underlying liver disease, such as jaundice or ascites, may be evident in patients with cirrhosis. Splenomegaly (enlarged spleen) may be palpable in cases of splenic sequestration. Lymphadenopathy (swollen lymph nodes) can suggest infections or lymphoma. Attention should be paid to signs of nutritional deficiencies in patients with eating disorders or alcoholism. A neurological examination is essential, particularly looking for impairment of proprioception (sense of body position) and ataxia (loss of coordination), which can suggest subacute combined degeneration of the spinal cord secondary to vitamin B12 (cobalamin) deficiency and macrocytic anemia. A positive Romberg test (difficulty maintaining balance with eyes closed) may also be indicative of B12 deficiency.
This initial assessment, combining history and physical findings, is crucial for narrowing down the differential diagnosis and guiding further investigations, just as initial troubleshooting helps a mechanic focus on specific areas of a car problem.
Evaluation and Diagnosis of Pancytopenia: A Step-by-Step Approach
Just as diagnosing a car problem involves a systematic series of tests and inspections, the evaluation of pancytopenia follows a structured approach to pinpoint the underlying cause. The initial workup is similar to a mechanic’s basic diagnostic checks and includes a complete blood count (CBC) along with a reticulocyte count. The CBC confirms the presence of pancytopenia by quantifying the levels of red blood cells, white blood cells, and platelets. The reticulocyte count helps determine if the pancytopenia is due to decreased production in the bone marrow. A low reticulocyte count suggests decreased production, while a high count might indicate increased peripheral destruction or loss. The mean corpuscular volume (MCV), a measure of red blood cell size, can provide clues; for example, a high MCV points towards megaloblastic anemia, often caused by vitamin B12 or folate deficiency.
A peripheral blood smear, analogous to visually inspecting car components, is a crucial next step. It allows for microscopic examination of blood cells to identify abnormal cells such as blasts (immature blood cells), dysplastic leukocytes (abnormally developed white blood cells), and other immature cells. The presence of these abnormal cells can be highly suggestive of specific underlying conditions (Table 3). Further investigations are then guided by these initial findings and may include:
- Bone Marrow Aspirate and Biopsy: This is a central investigation in pancytopenia diagnosis, akin to opening up the engine to examine its internal parts. Bone marrow aspiration and biopsy provide direct assessment of the bone marrow’s cellularity, maturation, and presence of abnormal cells or infiltration.
- Cytogenetic Testing: Techniques like fluorescent in situ hybridization (FISH) and karyotyping of bone marrow or peripheral blood are used to detect chromosomal abnormalities. This is similar to genetic testing in humans and can identify genetic mutations associated with certain types of leukemia and myelodysplastic syndromes.
- Flow Cytometry: Flow cytometry of bone marrow and/or peripheral blood analyzes cell surface markers to identify specific cell populations and diagnose hematologic malignancies, akin to identifying specific car parts through their unique identifiers.
- Molecular Studies: Molecular studies, such as mutation analysis and gene expression profiling, are used to detect specific genetic mutations and gene expression patterns associated with various hematologic disorders. This is like advanced diagnostic tools that pinpoint specific molecular defects.
- Vitamin B12 and Folate Levels: These blood tests assess for nutritional deficiencies that can cause megaloblastic anemia and pancytopenia.
- Liver Chemistry and Lactate Dehydrogenase (LDH): Liver function tests and LDH levels can provide insights into liver disease and hemolysis (red blood cell destruction), respectively, which can be associated with pancytopenia.
- Infectious Workup: Given the association of infections with pancytopenia, investigations for HIV, malaria, tuberculosis, and other relevant infections may be necessary, especially in endemic areas or based on patient risk factors.
In cases of pancytopenia following an acute viral infection, particularly if mild and resolving, extensive workup may be deferred, and follow-up blood counts can confirm resolution. Similarly, in severe sepsis, pancytopenia is often a consequence of the infection, and addressing the sepsis is the priority. Further evaluation for hepatitis, autoimmune conditions, or malignancies is warranted if suspected or if pancytopenia persists without a clear explanation. Serum calcium and parathyroid hormone levels can be checked, as hyperparathyroidism has been rarely linked to pancytopenia. A thyroid profile should also be considered, as both hyperthyroidism and hypothyroidism can be associated with pancytopenia.
Bone marrow aspiration and biopsy are typically performed if no specific etiology is identified through initial investigations. Bone marrow examination is diagnostic in approximately 75% of pancytopenia cases. The most common findings are hypoplastic marrow (reduced cellularity), megaloblastic anemia, and hematological malignancies. Pathological examination of the bone marrow biopsy is particularly helpful in diagnosing malignant etiologies, revealing clonal populations of cells, primary or secondary malignant cells, acellular marrow, fibroblasts, and granulomas indicative of tuberculosis, sarcoidosis, or fungal infections.
Abnormal Cells on Blood Smear and Associated Conditions: Table 3
| Abnormal Cell Type | Associated Conditions |
|---|---|
| Blasts | Acute Leukemia, Myelodysplastic Syndromes |
| Dysplastic WBCs | Myelodysplastic Syndromes, Megaloblastic Anemia |
| Atypical Lymphocytes | Viral Infections (EBV, CMV), Lymphoproliferative Disorders |
| Hairy Cells | Hairy Cell Leukemia |
| Schistocytes | Microangiopathic Hemolytic Anemia (MAHA) |
| Spherocytes | Hereditary Spherocytosis, Autoimmune Hemolytic Anemia |
| Sickle Cells | Sickle Cell Anemia |
Table 3: Abnormal Cells on Blood Smear with Associated Conditions. This table lists various abnormal cells that may be observed on a peripheral blood smear and the conditions they are commonly associated with, aiding in the differential diagnosis of pancytopenia.
Treatment and Management of Pancytopenia: Addressing the Root Cause
Just as car repairs target the specific malfunction, pancytopenia treatment is directed at the underlying etiology. Nutritional deficiencies, such as vitamin B12 or folate deficiency, are corrected through supplementation. Offending drugs suspected of causing pancytopenia should be immediately discontinued, similar to removing contaminated fuel from a car. Infections like HIV or tuberculosis require prompt initiation of appropriate antimicrobial therapy. Autoimmune conditions or malignancies necessitate specific treatments, such as immunosuppressants or chemotherapy, respectively. Aplastic anemia secondary to transient viral infections like parvovirus B19 often resolves spontaneously with supportive care. Severe aplastic anemia may require more intensive interventions, including hematopoietic stem cell transplantation or immunosuppressive therapy. Hematology referral is crucial for patients with aplastic anemia and other complex cases.
Supportive care plays a vital role in managing pancytopenia symptoms, akin to providing temporary fixes while awaiting permanent repairs. Red blood cell transfusions are used to treat anemia, alleviating symptoms and ensuring adequate oxygen delivery to vital organs. Platelet transfusions are indicated for severe thrombocytopenia (platelet count less than 10,000 per mcL) to prevent spontaneous bleeding, particularly intracranial hemorrhage. Prompt initiation of broad-spectrum antibiotics is recommended for patients with neutropenic fever or severe neutropenia (absolute neutrophil count less than 500 per ml) due to the high risk of sepsis.
Differential Diagnosis of Pancytopenia: Broadening the Scope
Similar to considering various potential causes for car trouble, the differential diagnosis of pancytopenia is broad, encompassing multiple conditions. Bone marrow disorders are prominent in the differential, including aplastic anemia, myelodysplastic syndromes, acute leukemia, myelofibrosis, megaloblastic anemia, paroxysmal nocturnal hemoglobinuria, and Fanconi anemia. Fanconi anemia is the most common congenital cause of bone marrow failure, inherited in an autosomal recessive pattern. In myelofibrosis, bone marrow cells are replaced by fibrotic tissue, hindering blood cell production. Malignancies such as lymphoma, multiple myeloma, and hairy cell leukemia can also manifest with pancytopenia. Non-bone marrow conditions in the differential include systemic lupus erythematosus and various infections (parvovirus B19, Epstein-Barr virus, HIV, hepatitis, leishmaniasis, tuberculosis, malaria, and histoplasmosis).
Prognosis of Pancytopenia: Predicting the Course
Just as predicting a car’s lifespan depends on the type and severity of its problems, the prognosis of pancytopenia is highly variable and depends on the underlying condition. In cases related to transient viral infections, the prognosis is generally excellent, with pancytopenia resolving spontaneously without specific intervention. The prognosis for myelodysplastic syndromes varies based on the severity of pancytopenia and the percentage of blasts in the bone marrow, ranging from indolent to aggressive forms. Pancytopenia induced by chemotherapy or certain medications (methotrexate, linezolid, anticonvulsants) is often reversible upon discontinuation of the offending agent.
Complications of Pancytopenia: Potential Risks
Pancytopenia carries significant risks and potential complications, much like ignoring car problems can lead to breakdowns or accidents. Increased risk of infections is a major complication due to leukopenia. Life-threatening anemia can develop due to red blood cell deficiency. Bleeding complications arise from thrombocytopenia. Patients presenting with fever and neutropenia require urgent broad-spectrum antibiotics and antifungals, along with pan cultures to identify the source of infection. Supportive transfusions with packed red blood cells and platelets are crucial in cases of severe anemia or thrombocytopenia with bleeding. Tumor lysis syndrome, a metabolic derangement, is a potential complication in patients receiving chemotherapy for bulky tumors like high-grade lymphoma and acute leukemia.
Consultations in Pancytopenia Management: The Team Approach
Managing pancytopenia effectively often requires a multidisciplinary team, similar to complex car repairs needing specialists in different areas. Hematology/oncology consultation is essential for all patients with pancytopenia to guide diagnosis and management. Infectious disease consultation is needed for patients with suspected or confirmed infections. Rheumatology consultation is necessary for patients with autoimmune conditions or medication-related issues. Endocrinology consultation is indicated for patients with thyroid disorders or hypercalcemia identified during the workup.
Deterrence and Patient Education: Prevention and Awareness
Patient education is crucial in mitigating risks associated with pancytopenia, much like educating drivers on car maintenance and safe driving practices. Patients should be educated about potential adverse reactions and toxicities of medications, including over-the-counter supplements. The importance of regular monitoring and blood work should be emphasized for patients on medications like methotrexate or linezolid that can cause pancytopenia. Patients with underlying hematologic malignancies should be informed about the risk of pancytopenia.
Patients diagnosed with pancytopenia should receive comprehensive counseling regarding the potential complications, including increased risk of infections, bleeding, and symptoms of anemia. They should be advised to avoid other medications that could worsen pancytopenia without consulting their healthcare provider.
Pearls and Other Critical Issues in Pancytopenia
Pancytopenia can present as a medical emergency in several scenarios:
- Neutropenia: New onset neutropenia or neutropenia with fever/infection requires immediate attention.
- Metabolic Emergencies: Symptomatic hyperkalemia, hypercalcemia, and tumor lysis syndrome are critical complications.
- Disseminated Intravascular Coagulation (DIC): A life-threatening clotting disorder.
- Hemophagocytic Lymphohistiocytosis (HLH): A severe hyperinflammatory syndrome.
- Abnormal Peripheral Blood Smear: Presence of microangiopathy or blasts on blood smear indicates serious conditions.
- Severe Aplastic Anemia: Represents bone marrow failure and requires urgent management.
- Symptomatic Anemia: Cardiac ischemia, hemodynamic instability, or worsening congestive heart failure due to anemia.
- Thrombocytopenia: Severely low platelet count (platelets < 20,000/mcL) with active bleeding or high risk of bleeding.
Enhancing Healthcare Team Outcomes in Pancytopenia Management
Effective pancytopenia management relies heavily on a collaborative interprofessional team approach, similar to a team of specialists working together on complex car repairs. While hospitalists or primary care providers often initiate the initial evaluation, involving hematologists/oncologists, rheumatologists, pathologists, radiologists, and pharmacists is crucial for optimal outcomes. Hematologists are central to diagnosis and management, performing bone marrow biopsies and guiding treatment strategies. Pathologists and hematologists collaborate closely in interpreting bone marrow findings. Rheumatologists manage pancytopenia secondary to autoimmune diseases or medication side effects. Pharmacists play a vital role in medication management, dose adjustments, and identifying drug-induced pancytopenia. Nurses are essential for patient monitoring, vital signs assessment (especially fever detection), patient education, and counseling regarding medication adverse effects.
Improved patient outcomes in pancytopenia management are achieved through prompt consultation with this interprofessional team, coordinated activity, and open communication to ensure accurate diagnosis and tailored treatment plans. This collaborative approach maximizes patient safety and optimizes outcomes in this complex hematologic condition.
Review Questions (Content from original article can be adapted here)
References (Keep original references)
1.Vargas-Carretero CJ, Fernandez-Vargas OE, Ron-Magaña AL, Padilla-Ortega JA, Ron-Guerrero CS, Barrera-Chairez E. Etiology and clinico-hematological profile of pancytopenia: experience of a Mexican Tertiary Care Center and review of the literature. Hematology. 2019 Dec;24(1):399-404. [PubMed: 30890036]
2.Das Makheja K, Kumar Maheshwari B, Arain S, Kumar S, Kumari S, Vikash The common causes leading to pancytopenia in patients presenting to tertiary care hospital. Pak J Med Sci. 2013 Sep;29(5):1108-11. [PMC free article: PMC3858928] [PubMed: 24353701]
3.Jain A, Naniwadekar M. An etiological reappraisal of pancytopenia – largest series reported to date from a single tertiary care teaching hospital. BMC Hematol. 2013 Nov 06;13(1):10. [PMC free article: PMC4177001] [PubMed: 24238033]
4.Gnanaraj J, Parnes A, Francis CW, Go RS, Takemoto CM, Hashmi SK. Approach to pancytopenia: Diagnostic algorithm for clinical hematologists. Blood Rev. 2018 Sep;32(5):361-367. [PubMed: 29555368]
5.Takeshima M, Ishikawa H, Kitadate A, Sasaki R, Kobayashi T, Nanjyo H, Kanbayashi T, Shimizu T. Anorexia nervosa-associated pancytopenia mimicking idiopathic aplastic anemia: a case report. BMC Psychiatry. 2018 May 25;18(1):150. [PMC free article: PMC5970484] [PubMed: 29801443]
6.Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. [PMC free article: PMC7166509] [PubMed: 32073213]
7.Al-Samkari H, Karp Leaf RS, Dzik WH, Carlson JCT, Fogerty AE, Waheed A, Goodarzi K, Bendapudi PK, Bornikova L, Gupta S, Leaf DE, Kuter DJ, Rosovsky RP. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020 Jul 23;136(4):489-500. [PMC free article: PMC7378457] [PubMed: 32492712]
8.Kasinathan G, Sathar J. Haematological manifestations, mechanisms of thrombosis and anti-coagulation in COVID-19 disease: A review. Ann Med Surg (Lond). 2020 Aug;56:173-177. [PMC free article: PMC7324342] [PubMed: 32637095]
9.Issa N, Lacassin F, Camou F. First case of persistent pancytopenia associated with SARS-CoV-2 bone marrow infiltration in an immunocompromised patient. Ann Oncol. 2020 Oct;31(10):1418-1419. [PMC free article: PMC7323636] [PubMed: 32615155]
10.Steensma DP. The Clinical Challenge of Idiopathic Cytopenias of Undetermined Significance (ICUS) and Clonal Cytopenias of Undetermined Significance (CCUS). Curr Hematol Malig Rep. 2019 Dec;14(6):536-542. [PubMed: 31696381]
11.Martín Pozuelo Ruiz de Pascual R, López Pardo P, López-Dóriga Bonnardeaux P. Pancytopenia during SARS-CoV-2 infection. Med Clin (Barc). 2020 Oct 23;155(8):364-365. [PMC free article: PMC7548061] [PubMed: 32753109]
12.Zhao Y, He J, Wang J, Li WM, Xu M, Yu X, Wu W, Sun C, Xu Z, Zhang W, Hu Y, Huang H. Development of pancytopenia in a patient with COVID-19. J Med Virol. 2021 Mar;93(3):1219-1220. [PMC free article: PMC7537507] [PubMed: 32990983]
13.Devitt KA, Lunde JH, Lewis MR. New onset pancytopenia in adults: a review of underlying pathologies and their associated clinical and laboratory findings. Leuk Lymphoma. 2014 May;55(5):1099-105. [PubMed: 23829306]
14.Khunger JM, Arulselvi S, Sharma U, Ranga S, Talib VH. Pancytopenia–a clinico haematological study of 200 cases. Indian J Pathol Microbiol. 2002 Jul;45(3):375-9. [PubMed: 12785191]
15.King KY, Goodell MA. Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune response. Nat Rev Immunol. 2011 Sep 09;11(10):685-92. [PMC free article: PMC4154310] [PubMed: 21904387]
16.Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ., HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. [PMC free article: PMC7270045] [PubMed: 32192578]
17.Zhan S, Cheng F, He H, Hu S, Feng X. Identification of transcobalamin deficiency with two novel mutations in the TCN2 gene in a Chinese girl with abnormal immunity: a case report. BMC Pediatr. 2020 Oct 06;20(1):460. [PMC free article: PMC7537950] [PubMed: 33023511]
18.Santiago-Rodríguez EJ, Mayor AM, Fernández-Santos DM, Hunter-Mellado RF. Profile of HIV-Infected Hispanics with Pancytopenia. Int J Environ Res Public Health. 2015 Dec 22;13(1):ijerph13010038. [PMC free article: PMC4730429] [PubMed: 26703689]
19.Tiresse N, Allaoui M. [Multifocal tuberculosis revealed by pancytopenia: about a case]. Pan Afr Med J. 2018;31:92. [PMC free article: PMC6462177] [PubMed: 31011393]
20.Achi HV, Ahui BJ, Anon JC, Kouassi BA, Dje-Bi H, Kininlman H. [Pancytopenia: a severe complication of miliary tuberculosis]. Rev Mal Respir. 2013 Jan;30(1):33-7. [PubMed: 23318187]
21.Sawada K, Takai A, Yamada T, Araki O, Yamauchi Y, Eso Y, Takahashi K, Shindo T, Sakurai T, Ueda Y, Seno H. Hepatitis-associated Aplastic Anemia with Rapid Progression of Liver Fibrosis Due to Repeated Hepatitis. Intern Med. 2020 Apr 15;59(8):1035-1040. [PMC free article: PMC7205540] [PubMed: 31875639]
22.Opie J, Omar F, Huang HC, Sandler L, Ross I. Primary hyperparathyroidism manifesting with pancytopenia. Pathology. 2017 Apr;49(3):326-329. [PubMed: 28267996]
23.Lim DJ, Oh EJ, Park CW, Kwon HS, Hong EJ, Yoon KH, Kang MI, Cha BY, Lee KW, Son HY, Kang SK. Pancytopenia and secondary myelofibrosis could be induced by primary hyperparathyroidism. Int J Lab Hematol. 2007 Dec;29(6):464-8. [PubMed: 17988303]
24.Hamid OA, Fadul AM, Batia TB, Yassin MA. Graves’ Disease-Related Pancytopenia Improved after Radioactive Iodine Ablation. Case Rep Oncol. 2020 Jan-Apr;13(1):295-298. [PMC free article: PMC7154234] [PubMed: 32308594]
25.Garla VV, Abdul Salim S, Yanes-Cardozo LL. Pancytopenia: a rare complication of Graves’ disease. BMJ Case Rep. 2018 Mar 09;2018 [PMC free article: PMC5847973] [PubMed: 29525760]
26.Jha A, Sayami G, Adhikari RC, Panta AD, Jha R. Bone marrow examination in cases of pancytopenia. JNMA J Nepal Med Assoc. 2008 Jan-Mar;47(169):12-7. [PubMed: 18552886]
27.Spivak JL. Masked megaloblastic anemia. Arch Intern Med. 1982 Nov;142(12):2111-4. [PubMed: 7138159]
28.Xiao N, Hao S, Zhang Y, Shao Z. Roles of immune responses in the pathogenesis of immunorelated pancytopenia. Scand J Immunol. 2020 Aug;92(2):e12911. [PubMed: 32474938]
29.Bagheri Z, Labbani-Motlagh Z, Mirjalili M, Karimzadeh I, Khalili H. Types and outcomes of cytopenia in critically ill patients. J Comp Eff Res. 2020 Jun;9(9):627-637. [PubMed: 32495631]
Disclosure: Shalini Chiravuri declares no relevant financial relationships with ineligible companies.
Disclosure: Orlando De Jesus declares no relevant financial relationships with ineligible companies.
