What Are the Causes of Pancytopenia?

Pancytopenia, also known as aplastic anemia (aplastic anemia), is a pancytopenia syndrome caused by bone marrow hematopoietic failure.

Pancytopenia

Pancytopenia, also known as aplastic anemia (aplastic anemia), is a pancytopenia syndrome caused by bone marrow hematopoietic failure.

Affected area

whole body

Related diseases

Benzene poisoning hyperthyroidism chronic renal failure

Related symptoms

Septicemia proteinuria

Affiliated Department

Department of Internal Medicine

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Basic dot red blood cell count

Divided into two categories of congenital and acquired, to obtain the vast majority of sexuality. Congenital aplastic anemia is rare and its main type is Fanconi anemia. Acquired aplastic anemia can be divided into primary and secondary types. The former is unknown, accounting for about 50% of acquired aplastic anemia. It can also be divided into acute and Chronic two types; severe aplastic anemia is classified abroad according to the severity, and the criteria for the latter must have two of the following three items: absolute value of neutrophils, bone marrow cell proliferation is lower than normal 25%, such as The clinical manifestations of anemia are mainly anemia, bleeding, and infection. The severity of clinical manifestations depends on the degree of hemoglobin, white blood cells, and thrombocytopenia, and is also related to the clinical type.

Acute aplastic anemia

Acute aplastic anemia is characterized by rapid onset, rapid progress, and short duration. Anemia is usually not obvious at the beginning of the onset. However, as the disease progresses, anemia progressively worsens, and many symptoms such as fatigue, dizziness, and palpitations are apparent. It is also difficult to improve. Bleeding and infection are often the main symptoms at the onset of bleeding. Almost every case has bleeding. The bleeding site is extensive. In addition to skin and mucous membranes (oral, nasal cavity, gums, bulbar conjunctiva) and other body surface bleeding, deep organ bleeding often occurs. Such as blood in the stool, hematuria, vaginal bleeding, fundus bleeding, and intracranial hemorrhage, the latter often endangers patients' lives. Infection occurs in more than half of the cases. Oropharyngeal infections, pneumonia, skin bloatedness, intestinal infections, and urinary tract infections are more common. In severe cases, sepsis can occur. The most common pathogenic bacteria are E. coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Infection often exacerbates bleeding and often causes death.

Chronic aplastic anemia

Chronic aplastic anemia is characterized by a slow onset of disease, a slow progression of the disease course, and a longer disease course. Anemia is the first and main manifestation. Transfusion can improve symptoms of anemia such as fatigue, dizziness, and palpitations. Bleeding is generally mild, mostly skin and mucosal bleeding, and deep bleeding is rare. There may be mild infection and fever in the course of the disease, which is more common in respiratory infections, and it is easier to control; if the infection is severe and persistently high fever, bone marrow failure often worsens and becomes severe aplastic anemia.

3. Aplastic anemia

(1) Paroxysmal nocturnal hemoglobinuria (PNH) / Aplastic anemia: There is a strong correlation between PNH and aplastic anemia. The two diseases often occur at the same time or in the same patient. The clinical characteristics are similar and both have whole blood cells. Decreased and low bone marrow hyperplasia, the disease has a regional tendency, the incidence in Asia is high, and it is effective for immunosuppressive therapy. PNH is characterized by intravascular hemolysis, venous thrombosis and bone marrow hematopoietic failure, and many patients die from thrombosis rather than bleeding complications.

(2) Hepatitis / Aplastic Syndrome: Aplastic anemia after acute viral hepatitis is not uncommon, and hundreds of cases have been reported so far. 2 to 9% of patients with aplastic anemia reported in the West have a history of hepatitis before, and the proportion in Asia may be higher. Although viral hepatitis can sometimes be combined with mild hemocytopenia, severe pancytopenia and hypomyeloplasia are uncommon, accounting for 2% of hepatitis B in children. In patients with fulminant sero-negative hepatitis leading to liver failure, a third will eventually develop aplastic anemia. There are several characteristics of aplastic anemia after hepatitis:

Frequently occurs within 1 to 2 months after viral hepatitis, severe pancytopenia occurs during the period of inflammation recovery, and mild hemocytopenia may occur during the viral hepatitis inflammation period, such as granulocytes, thrombocytopenia, and large red blood cells. Typical lymphocytosis, etc., similar to mild aplastic anemia. The prognosis is very poor, and the mortality rate can reach 90% within 1 year;

The virus that causes post-hepatitis aplastic anemia is not very clear. Almost all studies have shown that the virus is non-A, non-B, non-C, and non-G. Patients with aplastic anemia combined with hepatitis C and hepatitis G viral hepatitis are common, and they are mostly considered to be caused by repeated blood transfusions, rather than the cause of aplastic anemia. Serum-negative acute viral hepatitis and hepatitis C are significantly different clinically, that is, parental contact is not the same. Risk factors, patients with abnormal liver function in the acute phase are very serious, and late complications are common. For hepatitis / aplastic syndrome, allogeneic bone marrow transplantation should be preferred. For patients with marked immune activation markers, intensive immunosuppressive therapy is often effective.

(3) Aplastic anemia in pregnancy: Rare, it is unclear whether pregnancy is a predisposing factor. Hypomyeloplasia during pregnancy is relatively common, with pancytopenia often occurring at the beginning of pregnancy, and recovery after childbirth or termination of pregnancy, but a few pregnancy complicated with aplastic anemia can continue into postpartum. The survival rate of pregnancy combined with aplastic anemia is 53% for mothers and 75% for babies. 69% of patients have a smooth pregnancy. Therefore, intermittent blood transfusion can be used for mothers who continue to conceive, but pregnancy should be terminated when the condition worsens.

(4) Aplastic anemia after infectious mononucleosis: Infectious mononucleosis caused by acute EB virus infection is often accompanied by granulocytopenia and other hematological abnormalities, but aplastic anemia is rare. Because EB virus infection is the most common viral disease, many people have clinical symptoms that are not obvious. Whole blood cell reduction can be the main manifestation of early or recovery period of some infectious mononucleosis. In some patients, the blood symptoms can recover on their own. . Epstein-Barr virus has been detected in bone marrow hematopoietic cells in patients with idiopathic aplastic anemia, so the incidence of aplastic anemia after EB virus infection may be higher than previously expected. Antiviral therapy is effective for some patients with aplastic anemia after EB virus infection, and immunosuppressive therapy such as corticosteroids and ATG is also effective for some patients. It should be applied early in the course of the disease.

(5) Hematopoietic syndrome / Aplastic syndrome: Patients with hematopoietic syndrome have low myelodysplasia, and may also change from active myelodysplasia to low hyperplasia. Three-line cytopenias were present in 74% of patients with anemia, 91% had thrombocytopenia, and 65% had neutropenia. Unlike typical aplastic anemia, patients with hematopoietic syndrome / aplastic anemia have systemic immunodeficiency, malignancy, and infection. Viral infections are most common in infections, often herpes viruses, especially Epstein-Barr virus, others such as cytomegalovirus, herpes simplex virus, varicella-zoster virus, B19 parvovirus, HIV-1, followed by bacterial and protozoal infections Rejection after bone marrow transplantation can be complicated by hematopoietic cell syndrome. Diagnosis is based on a tissue biopsy and a bone marrow smear. Immune system activation is common in haemophilic syndrome associated with viral infections, such as increased levels of soluble receptors for peripheral blood IFN-gamma ;, TNF-alpha ;, IL-6 and IL-2, increased CD8-negative cells, and T cells In vitro culture produces IFN-gamma; it also increases significantly. The clinical application of cyclosporine A (CsA) is also effective, which also shows that T cell-mediated immune enhancement is the pathogenesis of hematopoietic failure.

(6) Graft-versus-host disease after transfusion: Aplastic anemia is a common fatal complication of graft-versus-host disease caused by blood transfusion. Children with innate immunodeficiency, cancer after chemotherapy, and leukemia patients who have received adoptive immunity in recent years, a small amount of donor lymphocytes is enough to produce graft-versus-host disease, and it is resistant to immunosuppressive therapy. The common hematological manifestations are Reduced whole blood cells and low bone marrow hyperplasia.

(7) Connective tissue disease: Aplastic anemia may be a clinical manifestation of eosinophilic fasciitis. Eosinophilic fasciitis is a serious connective tissue disease mainly manifested by skin sclerosis. Its pathology is subcutaneous and fascial fibrosis, clinical manifestations are skin sclerosis, eosinophilia, and high gamma; Proteinemia, ESR increases faster, and responds well to corticosteroid therapy. In addition, systemic lupus erythematosus and rheumatoid arthritis have been reported with aplastic anemia, but because of common immunosuppressive treatment, it is easy to be confused with drug side effects. ^[1]

The diagnostic criteria for aplastic anemia revised by the Fourth National Conference on Aplastic Anemia in 1987 are as follows:

Whole blood cells decrease, and the absolute value of reticulocytes decreases.

Generally no splenomegaly.

Bone marrow examination shows reduced or severely reduced hyperplasia in at least one part (if the proliferation is active, megakaryocytes should be significantly reduced, and non-hematopoietic cells should be seen in the bone marrow granules. Those with conditions should be examined for bone marrow biopsy).

Can exclude other diseases that cause pancytopenia, such as paroxysmal nocturnal hemoglobinuria, refractory anemia in myelodysplastic syndrome, acute hematopoiesis, myelofibrosis, acute leukemia, and malignant histiocytosis.

General anti-anemia drug treatment is ineffective.

The basis for the diagnosis of aplastic anemia proposed by the Institute of Hematology of the Chinese Academy of Medical Sciences in 1964 was established in 1987 as the current diagnostic standard for aplastic anemia in China after more than 20 years of clinical practice in China and after two revisions. The specific content is as follows.

1. Whole blood cells decrease, and the absolute value of reticulocytes decreases.

2. Generally without splenomegaly.

3. Hyperplasia or severe reduction in at least one part of the bone marrow examination.

4. Can exclude other diseases that cause pancytopenia, such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, acute hematopoiesis, myelofibrosis, acute leukemia, and malignant histiocytosis.

5. General antianemia drug treatment is ineffective

(1) Acute aplastic anemia (AAA), also known as severe aplastic anemia (SAA):

Clinical manifestations: acute onset, anemia is progressively worsening, often accompanied by severe infection, visceral bleeding.

Hematology: In addition to the rapid decline in hemoglobin, 2 of the following 3 items are required:

A. Reticulocyte

B. Leukocytes are significantly reduced and neutrophils

C. Platelets

bone marrow image:

A. Reduction of multi-site hyperplasia: The three lines of hematopoietic cells are significantly reduced, and non-hematopoietic cells are increased. If hyperplasia is active, lymphocytes must be increased.

B. Small non-hematopoietic cells and adipocytes increase in bone marrow.

(2) Chronic Aplastic Anemia (CAA):

Clinical manifestations: slow onset, mild anemia, infection, and bleeding.

Hematology: Hemoglobin decreases slowly, and reticulocytes, white blood cells, neutrophils, and platelet values are often higher than those of acute aplastic anemia.

bone marrow image:

A. Reduction of tertiary or secondary lines: Reduced proliferation in at least one part. For example, if the proportion of late red in carbon nuclei is often increased in proliferative active red lines, megakaryocytes are significantly reduced.

B. Small bone marrow adipocytes and non-hematopoietic cells increase.

(3) If the condition changes during the course of the disease: the clinical manifestations, blood and bone marrow are the same as those of acute aplastic anemia, and it is called severe aplastic anemia type II (SAA).

At present, the diagnostic criteria for severe aplastic anemia (SAA) proposed by Camitta (1976) are used abroad: 70% of peripheral blood neutrophils can be diagnosed as SAA; those who do not meet the above criteria are mild aplastic anemia (MAA). In recent years, many scholars have no difficulty in diagnosing typical cases of granulocytes. It can be determined based on clinical manifestations of anemia, bleeding, infection, peripheral blood whole blood cells, reduced bone marrow hyperplasia, and exclusion of other diseases that cause pancytopenia. diagnosis. A few atypical cases can be identified by observing morbid hematopoietic, bone marrow biopsy, hematopoietic progenitor cell culture, hemolysis test, chromosome, oncogene, and nuclide bone marrow scan.

1. Paroxysmal nocturnal hemoglobinuria (PNH) is difficult to distinguish from non-seizure type. However, the disease has less bleeding and infection, less reticulocytes than normal, more active hyperplasia of bone marrow, more obvious proliferation of juvenile red blood cells, a positive hemosiderin test (Ruos), and an acidic serum hemolysis test (Ham ) And snake venom test (CoF) are more positive, red blood cell complement detection test (mCLST), CD55, CD59 and other can detect PNH red blood cells, N-ALP decreased, plasma and red blood cell cholinesterase significantly reduced.

2. Differentiation between myelodysplastic syndrome (MDS) and refractory anemia (RA) in MDS is difficult. However, the disease is characterized by pathological hematopoiesis. Peripheral blood often shows uneven red blood cell size, and large red blood cells, nucleated red blood cells, and monocytes are easily seen. Immature granulocytes and deformed platelets are seen. Myeloid hyperplasia is more active, and there are secondary or tertiary pathological hematopoiesis. Giant juveniles and multinucleated red blood cells are more common. There are more young and medium granules, nuclear plasma development is imbalanced, and abnormal nuclear or excessive leaves are visible. There are many megakaryocytes, and lymphoid small megakaryocytes are more common. Histochemistry shows that erythrocyte glycogen (PAS) is positive, ring-shaped iron granulocytes are increased, and small meganucleases are positive. It can be further identified based on bone marrow biopsy, leukemia progenitor cell culture (CFU-L), chromosome, and oncogene tests.

3. Acute hematopoietic stagnation is often caused by infection and drugs. Children with malnutrition-related illnesses are often accompanied by high fever, anemia is severe, progress is rapid, and many are misdiagnosed as acute aplastic anemia. The following characteristics are helpful to identify: the anemia is heavy, the reticulocytes can be 0, and the granulocytes are reduced, but the platelet reduction is not obvious, and the bleeding is light; the bone marrow hyperplasia is more active, the second or third line is reduced, but The reduction is caused by huge primitive red blood cells at the end of the film; The condition is self-limiting and requires no special treatment and can be recovered in 2 to 6 weeks; The serum copper is significantly increased and the red blood cell copper is reduced.

4. Myelofibrosis (MF)

Chronic cases often have splenomegaly, immature granulocytes and nucleated red blood cells can be seen in peripheral blood, bone marrow puncture multiple dry draws, and bone marrow biopsy showed significant proliferation of collagen fibers and / or reticular fibers.

5. Acute Leukemia (AL)

In particular, hypoproliferative AL can be a chronic process with enlarged liver, spleen, and lymph nodes, reduced whole blood cells in peripheral blood, and reduced myeloproliferative disease, which is easily confused with aplastic anemia. The blood and multiple bone marrow images should be carefully observed, and a significant increase in primordial granules, single, or primordial lymphocytes can be found. A bone marrow biopsy can also help define the diagnosis.

6. Malignant histiocytosis (MH)

Often accompanied by non-infectious high fever, progressive failure, enlarged liver, spleen, and lymph nodes, severe jaundice and bleeding, marked reduction in peripheral blood whole blood cells, and abnormal tissue cells. Multi-site bone marrow examination can find abnormal tissue cells, often phagocytosis.

7. Pure red blood cell aplastic anemia

Whole blood cells reduce the risk of aplastic anemia and acute hematopoiesis of hemolytic anemia, which can be seen as whole blood cell reduction, acute onset, clear causes, and self-relief after removal. Giant primary red blood cells can appear in the bone marrow. Chronic acquired pure red aplastic anemia, if there is a slight decrease in white blood cells and platelets, should be distinguished from chronic aplastic anemia.

Splenectomy improves the infection, lower extremity ulcers, and granulocytopenia, but has no effect on arthritis.

Preoperative preparation:

1. For patients with portal hypertension, liver function should be improved and bleeding tendency should be corrected before surgery.

2. For some severe anemia, splenectomy should be performed after repeated blood transfusions.

3. For long-term use of hormones, antibiotics should be used prophylactically.

4. Preparing for general surgery before abdominal surgery.

Anesthesia requirements:

Endotracheal anesthesia.

Points to note during surgery:

1. Surgery can take an L-shaped incision under the left costal margin or upper abdomen, and the surgical field is fully exposed.

2. The spleen artery should be ligated before incision.

3. After splenectomy, a drainage tube should be placed in the spleen fossa.

4. Patients with hematological diseases must remove the paraspleen together.

5. Be careful not to damage the tail of the pancreas when removing the spleen to avoid pancreatic fistula after operation.

Postoperative management:

1. Follow the general abdominal surgery.

2. Drainage tube is generally removed 24 to 48 hours after surgery.

3. Check the white blood cells and platelets daily after the operation. When platelets exceed (0.8 to 1) 1012 / L after surgery, anticoagulation therapy should be performed.