Laboratory tests might include: full blood count, liver enzymes, renal function and erythrocyte sedimentation rate.

If the cause for the high platelet count remains unclear, bone marrow biopsy is often undertaken, to differentiate whether the high platelet count is reactive or essential.

Often, no treatment is required or necessary for reactive thrombocytosis. In cases of reactive thrombocytosis of more than 1,000x10/L, it may be considered to administer daily low dose aspirin (such as 65 mg) to minimize the risk of stroke or thrombosis.

However, in primary thrombocytosis, if platelet counts are over 750,000 or 1,000,000, and especially if there are other risk factors for thrombosis, treatment may be needed. Selective use of aspirin at low doses is thought to be protective. Extremely high platelet counts in primary thrombocytosis can be treated with hydroxyurea (a cytoreducing agent) or anagrelide (Agrylin).

In Jak-2 positive disorders, ruxolitinib (Jakafi) can be effective.

Generally accepted reference range for absolute neutrophil count (ANC) in adults is 1500 to 8000 cells per microliter (µl) of blood. Three general guidelines are used to classify the severity of neutropenia based on the ANC (expressed below in cells/µl):

- Mild neutropenia (1000 <= ANC < 1500): minimal risk of infection

- Moderate neutropenia (500 <= ANC < 1000): moderate risk of infection

- Severe neutropenia (ANC < 500): severe risk of infection.

Each of these are either derived from laboratory tests or via the formula below:

ANC = formula_1

Treatment of asymptomatic congenital dysfibrinogenemia depends in part on the expectations of developing bleeding and/or thrombotic complications as estimated based on the history of family members with the disorder and, where available, determination of the exact mutation causing the disorder plus the propensity of the particular mutation type to develop these complications. In general, individuals with this disorder require regular follow-up and multidiscipline management prior to surgery, pregnancy, and giving childbirth. Women with the disorder appear to have an increased rate of miscarriages and all individuals with fibrinogen activity in clotting tests below 0.5 grams/liter are prone to bleeding and spontaneous abortions. Women with multiple miscarriages and individuals with excessively low fibrinogen activity levels should be considered for prophylaxis therapy with fibrinogen replacement during pregnancy, delivery, and/or surgery.

Diagnosis of acquired dysfibrinogenemia uses the same laboratory tests that are used for congenital dysfibrinogenemia plus evidence for an underlying causative disease.

The overproduction of red blood cells may be due to a primary process in the bone marrow (a so-called myeloproliferative syndrome), or it may be a reaction to chronically low oxygen levels or, rarely, a malignancy. Alternatively, additional red blood cells may have been received through another process—for example, being over-transfused (either accidentally or, as blood doping, deliberately) or being the recipient twin in a pregnancy, undergoing twin-to-twin transfusion syndrome.

Secondary polycythemia is caused by either natural or artificial increases in the production of erythropoietin, hence an increased production of erythrocytes. In secondary polycythemia, 6 to 8 million and occasionally 9 million erythrocytes may occur per millimeter of blood. Secondary polycythemia resolves when the underlying cause is treated.

Secondary polycythemia in which the production of erythropoietin increases appropriately is called physiologic polycythemia.

Conditions which may result in a physiologically appropriate polycythemia include:

- Altitude related - This physiologic polycythemia is a normal adaptation to living at high altitudes (see altitude sickness). Many athletes train at high altitude to take advantage of this effect — a legal form of blood doping. Some individuals believe athletes with primary polycythemia may have a competitive advantage due to greater stamina. However, this has yet to be proven due to the multifaceted complications associated with this condition.

- Hypoxic disease-associated - for example in cyanotic heart disease where blood oxygen levels are reduced significantly, may also occur as a result of hypoxic lung disease such as COPD and as a result of chronic obstructive sleep apnea.

- Iatrogenic - Secondary polycythemia can be induced directly by phlebotomy (blood letting) to withdraw some blood, concentrate the erythrocytes, and return them to the body.

- Genetic - Heritable causes of secondary polycythemia also exist and are associated with abnormalities in hemoglobin oxygen release. This includes patients who have a special form of hemoglobin known as Hb Chesapeake, which has a greater inherent affinity for oxygen than normal adult hemoglobin. This reduces oxygen delivery to the kidneys, causing increased erythropoietin production and a resultant polycythemia. Hemoglobin Kempsey also produces a similar clinical picture. These conditions are relatively uncommon.

Conditions where the secondary polycythemia is not as a result of physiologic adaptation and occurs irrespective of body needs include:

- Neoplasms - Renal-cell carcinoma or liver tumors, von Hippel-Lindau disease, and endocrine abnormalities including pheochromocytoma and adrenal adenoma with Cushing's syndrome.

- People whose testosterone levels are high because of the use of anabolic steroids, including athletes who abuse steroids, or people on testosterone replacement for hypogonadism or transgender hormone replacement therapy, as well as people who take erythropoietin, may develop secondary polycythemia.

Neutropenia that is developed in response to chemotherapy typically becomes evident in seven to fourteen days after treatment. Conditions that indicate the presence of neutropenic fever are implanted devices; leukemia induction; the compromise of mucosal, mucociliary and cutaneous barriers; a rapid decline in absolute neutrophil count, duration of neutropenia >7–10 days, and other illnesses that exist in the patient.

Signs of infection in patients can be subtle. Fevers are a common and early observation. Sometimes overlooked is the presence of hypothermia, which can be present in sepsis. Physical examination and accessing the history and physical examination is focussed on sites of infection. Indwelling line sites, areas of skin breakdown, sinuses, nasopharynx, bronchi and lungs, alimentary tract, and skin are assessed.

The diagnosis of neutropenia is done via the low neutrophil count detection on a full blood count. Generally, other investigations are required to arrive at the right diagnosis. When the diagnosis is uncertain, or serious causes are suspected, bone marrow biopsy may be necessary. Other investigations commonly performed: serial neutrophil counts for suspected cyclic neutropenia, tests for antineutrophil antibodies, autoantibody screen (and investigations for systemic lupus erythematosus), vitamin B and folate assays. Rectal examinations are usually not performed due to the increased risk of introducing bacteria into the blood stream and the possible development of rectal abscesses. A routine chest X-ray and urinalysis may be can not be relied upon or considered normal due to the absence of neutrophils.

The following findings may be present:

- Increased red cell breakdown

- Elevated serum bilirubin (unconjugated)

- Excess urinary urobilinogen

- Reduced plasma haptoglobin

- Raised serum lactic dehydrogenase (LDH)

- Hemosiderinuria

- Methemalbuminemia

- Spherocytosis

- Increased red cell production:

- Reticulocytosis

- Erythroid hyperplasia of the bone marrow

- Specific investigations

- Positive direct Coombs test

Sideroblastic anemias are often described as responsive or non-responsive in terms of increased hemoglobin levels to pharmacological doses of vitamin B.

1- Congenital: 80% are responsive, though the anemia does not completely resolve.

2- Acquired clonal: 40% are responsive, but the response may be minimal.

3- Acquired reversible: 60% are responsive, but course depends on treatment of the underlying cause.

Severe refractory sideroblastic anemias requiring regular transfusions and/or that undergo leukemic transformation (5-10%) significantly reduce life expectancy.

Diagnosis is made by first ruling out other causes of hemolytic anemia, such as G6PD, thalassemia, sickle-cell disease, etc. Clinical history is also important to elucidate any underlying illness or medications that may have led to the disease.

Following this, laboratory investigations are carried out to determine the etiology of the disease. A positive DAT test has poor specificity for AIHA (having many differential diagnoses); so supplemental serological testing is required to ascertain the cause of the positive reaction. Hemolysis must also be demonstrated in the lab. The typical tests used for this are a complete blood count (CBC) with peripheral smear, bilirubin, lactate dehydrogenase (LDH) (in particular with isoenzyme 1), haptoglobin and urine hemoglobin.

The blood count typically shows decreased numbers of blood cells—including a decreased amount of circulating red blood cells, white blood cells, and platelets.

The bone marrow may show hemophagocytosis.

The liver function tests are usually elevated. A low level of the protein albumin in the blood is common.

The serum C reactive protein, erythrocyte sedimentation rate, and ferritin level are markedly elevated. In children, a ferritin above 10000 is very sensitive and specific for the diagnosis of HLH, however, the diagnostic utility for ferritin is less for adult HLH patients.

The serum fibrinogen level is usually low and the D-dimer level is elevated.

The sphingomyelinase is elevated.

Bone marrow biopsy shows histiocytosis.

Ringed sideroblasts are seen in the bone marrow.

The anemia is moderate to severe and dimorphic. Microscopic viewing of the red blood cells will reveal marked unequal cell size and abnormal cell shape. Basophilic stippling is marked and target cells are common. Pappenheimer bodies are present in the red blood cells. The mean cell volume is commonly decreased (i.e., a microcytic anemia), but MCV may also be normal or even high. The RDW is increased with the red blood cell histogram shifted to the left. Leukocytes and platelets are normal. Bone marrow shows erythroid hyperplasia with a maturation arrest.

In excess of 40% of the developing erythrocytes are ringed sideroblasts. Serum iron, percentage saturation and ferritin are increased. The total iron-binding capacity of the cells is normal to decreased. Stainable marrow hemosiderin is increased.

The current (2008) diagnostic criteria for HLH are

1. A molecular diagnosis consistent with HLH. These include the identification of pathologic mutations of PRF1, UNC13D, or STX11.

OR

2. Fulfillment of five out of the eight criteria below:

- Fever (defined as a temperature >100.4 °F, >38 °C)

- Enlargement of the spleen

- Decreased blood cell counts affecting at least two of three lineages in the peripheral blood:

- Haemoglobin <9 g/100 ml (in infants <4 weeks: haemoglobin <10 g/100 ml) (anemia)

- Platelets <100×10/L (thrombocytopenia)

- Neutrophils <1×10/L (neutropenia

- High blood levels of triglycerides (fasting, greater than or equal to 265 mg/100 ml) and/or decreased amounts of fibrinogen in the blood (≤ 150 mg/100 ml)

- Ferritin ≥ 500 ng/ml

- Haemophagocytosis in the bone marrow, spleen or lymph nodes

- Low or absent natural killer cell activity

- Soluble CD25 (soluble IL-2 receptor) >2400 U/ml (or per local reference laboratory)

In addition, in the case of familial HLH, no evidence of malignancy should be apparent.

It should be noted that not all five out of eight criteria are required for diagnosis of HLH in adults, and a high index of suspicion is required for diagnosis as delays results in increased mortality. The diagnostic criteria were developed in pediatric populations and have not been validated for adult HLH patients. Attempts to improve diagnosis of HLH have included use of the HScore, which can be used to estimate an individual's risk of HLH.

Fibrinogen disorders are set of hereditary or acquired abnormalities in the quantity and/or quality of circulating fibrinogens. The disorders may lead to pathological bleeding and/or blood clotting or the deposition of fibrinogen in the liver, kidneys, or other organs and tissues. These disorders include:

- Congenital afibrinogenemia, an inherited blood disorder in which blood does not clot normally due to the lack of fibrinogen; the disorder causes abnormal bleeding and thrombosis.

- Congenital hypofibrinogenemia, an inherited disorder in which blood may not clot normally due to reduced levels of fibrinogen; the disorder may cause abnormal bleeding and thrombosis.

- Fibringogen storage disease, a form of congenital hypofibrinogenemia in which specific hereditary mutations in fibrinogen cause it to accumulate in, and damage, liver cells. The disorder may lead to abnormal bleeding and thrombosis but also to cirrhosis.

- Congenital dysfibrinogenemia, an inherited disorder in which normal levels of fibrinogen composed at least in part of a dysfunctional fibrinogen may cause abnormal bleeding and thrombosis.

- Hereditary fibrinogen Aα-Chain amyloidosis, a form of dysfibrinogenemia in which certain fibrinogen mutations cause blood fibrinogen to accumulate in the kidney and cause one type of familial renal amyloidosis; the disorder is not associated with abnormal bleeding or thrombosis.

- Acquired dysfibrinogenemia, a disorder in which normal levels of fibrinogen are composed at least in part of a dysfunctional fibrinogen due to an acquired disorder (e.g. liver disease) that leads to the synthesis of an incorrectly glycosylated (i.e. wrong amount of sugar residues) added to an otherwise normal fibrinogen. The incorrectly glycosalated fibrinogen is dysfunctional and may cause pathological episodes of bleeding and/or blood clotting.

- Congenital hypodysfibrinogenemia, an inherited disorder in which low levels of fibrinogen composed at least in part of a dysfunctional fibrinogen may cause pathological episodes of bleeding or blood clotting.

- Cryofibrinogenemia, an acquired disorder in which fibrinogen precipitates at cold temperatures and may lead to the intravascular precipitation of fibrinogen, fibrin, and other circulating proteins thereby causing the infarction of various tissues and bodily extremities.

Testing the general population under the age of 40 without symptoms is of unclear benefit.

Myomatous erythrocytosis syndrome describes an excessive erythrocyte (red blood cells) production, occurring in about 0.5% of individuals affected by uterine leiomyomas (fibroids). This syndrome is believed to be caused by increased erythropoietin (EPO) production by the kidneys or by the leiomyomas themselves.

Activated protein C resistance (APCR) is a hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). This results in an increased risk of venous thrombosis, which can cause problems with circulation, such as pulmonary embolism.

The disorder can be acquired or inherited, the hereditary form having an autosomal dominant inheritance pattern.

An estimated 64 percent of patients with venous thromboembolism may have activated protein C resistance.

The diagnosis of T cell deficiency can be ascertained in those individuals with this condition via the following:

- Delayed hypersensitivity skin test

- T cell count

- Detection via culture(infection)

In terms of diagnosis of "humoral immune deficiency" depends upon the following:

- Measure "serum immunoglobulin levels"

- B cell count

- Family medical history

Treatment for "B cell deficiency"(humoral immune deficiency) depends on the cause, however generally the following applies:

- Treatment of infection(antibiotics)

- Surveillance for malignancies

- Immunoglobulin replacement therapy

In terms of the management of T cell deficiency for those individuals with this condition the following can be applied:

- Killed vaccines should be used(not "live vaccines" in T cell deficiency)

- Bone marrow transplant

- Immunoglobulin replacement

- Antiviral therapy

- Supplemental nutrition

In 2010, the case of a man with unexplained erythrocytosis and perinephric fluid collection as main features was described in the Case Records of the Massachusetts General Hospital. As a consequence two strikingly similar cases were identified and a review of the literature revealed three more patients with similar characteristics.

As of December 2014, a total of 9 patients worldwide with the TEMPI syndrome have been identified (D.B.Sykes, Personal Communication).

In terms of their therapy:

- Untreated: 2 patients

- Velcade alone: 5 patients

- Immediate autologous transplant: 1 patient

- Velcade followed by Velcade/Lenalidomide followed by autologous transplant: 1 patient

The diagnosis of the disease is mainly clinical (see diagnostic criteria). A laboratory workup is needed primarily to investigate for the presence of associated disorders (metabolic, autoimmune, and renal diseases).

- Every patient should have a fasting blood glucose and lipid profile, creatinine evaluation, and urinalysis for protein content at the first visit, after which he/she should have these tests on a regular basis.

- Although uncommon, lipid abnormalities can occur in the form of raised triglyceride levels and low high-density lipoprotein cholesterol levels.

- Patients usually have decreased serum C3 levels, normal levels of C1 and C4, and high levels of C3NeF (autoantibody), which may indicate the presence of renal involvement.

- Antinuclear antibodies (ANA) and antidouble-stranded deoxyribonucleic acid (DNA) antibodies have reportedly been observed in some patients with acquired partial lipodystrophy.

- A genetic workup should be performed if the familial form of lipodystrophy is suggested.

Laboratory work for associated diseases includes:

- Metabolic disease - fasting glucose, glucose tolerance test, lipid profile, and fasting insulin to characterize the insulin resistance state; free testosterone (in women) to look for polycystic ovary syndrome.

- Autoimmune disease - ANA, antidouble-stranded DNA, rheumatoid factor, thyroid antibodies, C3, and C3NeF.

As a confirmatory test, whole-body MRI usually clearly demonstrates the extent of lipodystrophy. MRI is not recommended on a routine basis.