Elevated haemoglobin A2 level is seen in beta thalassaemia trait, whereas, it is typically low in iron deficiency anaemia unless the patient has received a recent blood transfusion.

Low mean corpuscular volume (MCV) and reduced haematocrit (Ht) are encountered in both conditions. Peripheral blood smear is grossly abnormal in both beta thalassaemia and severe iron deficiency anaemia, showing bizarre morphology, target cells, and a small number of nucleated red blood cells.

Neutrophilia is also commonly associated with polycythaemia vera.

Polycythaemia vera (PV), also known as polycythaemia rubra vera, is a myeloproliferative disorder caused by clonal proliferation of marrow stem cells leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has peak incidence in the sixth decade of life, with typical features including hyperviscosity, pruritus, splenomegaly, haemorrhage (secondary to abnormal platelet function), and plethoric appearance.

Some management options of PV include lose-dose aspirin, venesection (first-line treatment), hydroxyurea (slightly increased risk of secondary leukaemia), and radioactive phosphorus (P-32) therapy.

In PV, thrombotic events are a significant cause of morbidity and mortality. 5–15% of the cases progress to myelofibrosis or AML. The risk of having AML is increased with chemotherapy treatment.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition that can affect nearly any organ system: the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, meninges, aorta, breast, prostate, thyroid, pericardium, and skin. The histopathological features are similar across organs, regardless of the site. IgG4-RD is analogous to sarcoidosis, in which diverse organ manifestations are linked by similar histopathological characteristics. Raised concentrations of IgG4 in tissue and serum can be helpful in diagnosing IgG4 disease, but neither is a specific diagnostic marker.

Some IgG4-RDs are:
1. Autoimmune pancreatitis
2. Riedel’s Thyroiditis
3. Mediastinal and Retroperitoneal Fibrosis
4. Periaortitis/periarteritis/Inflammatory aortic aneurysm
5. Kuttner Tumour (submandibular glands)
6. IgG4-related Mikulicz disease (lacrimal, parotid, and submandibular glands)

Prostate cancer is the most common primary tumour that metastasises to the bone.

Most common tumours causing bone metastasis (in descending order):
1. Prostate (32%)
2. Breast (22%)
3. Kidneys (16%)
4. Lungs
5. Thyroid

Most common sites of bone metastasis (in descending order):
1. Spine
2. Pelvis
3. Ribs
4. Skull
5. Long bones

Methemoglobinemia is a rare condition in which the haemoglobin iron is in oxidized or ferric state (Fe3+) and cannot reversibly bind oxygen. Normally, the conversion of ferrous form of iron (Fe2+) to its ferric form (Fe3+) is regulated by NADH methaemoglobin reductase, which results in the reduction of methaemoglobin to haemoglobin. Disruption in the enzyme leads to increased methaemoglobin in the blood. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxygen-haemoglobin dissociation curve is shifted to the left.

Methemoglobinemia can occur due to congenital or acquired causes. Congenital causes include haemoglobin variants such as HbM and HbH, and deficiency of NADH methaemoglobin reductase. Acquired causes are drugs (e.g. sulphonamides, nitrates, dapsone, sodium nitroprusside, and primaquine) and chemicals (such as aniline dyes).

The features of methemoglobinemia are cyanosis, dyspnoea, anxiety, headache, severe acidosis, arrhythmias, seizures, and loss of consciousness. Patients have normal pO2 but oxygen saturation is decreased. Moreover, presence of chocolate-brown coloured arterial blood (colour does not change with addition of O2) and brown urine also point towards the diagnosis of methemoglobinemia.

Generally, underlying causes of confusion need to be looked for and treated as appropriate, for example, hypercalcaemia, infection, urinary retention, and medication. If specific treatments fail, the following may be tried:

1. First choice: haloperidol
2. Other options: chlorpromazine, levomepromazine

In the terminal phase of the illness, agitation or restlessness is best treated with midazolam.

Rasburicase should be given prior to chemotherapy in order to reduce the risk of tumour lysis syndrome (TLS). Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin. Allantoin is 5–10 times more soluble than uric acid, hence, renal excretion is more effective.

TLS is a potentially fatal condition occurring as a complication during the treatment of high-grade lymphomas and leukaemias. It occurs from the simultaneous breakdown (lysis) of the tumour cells and subsequent release of chemicals into the bloodstream. This leads to hyperkalaemia and hyperphosphatemia in the presence of hyponatraemia. TLS can occur in the absence of chemotherapy, but it is usually triggered by the introduction of combination chemotherapy. Awareness of the condition is critical for its prophylactic management.

Burkitt lymphoma is a high-grade B-cell neoplasm. There are two major forms:
1. Endemic (African) form: typically involves maxilla or mandible.
2. Sporadic form: abdominal (e.g. ileocaecal) tumours are the most common form. More common in patients with HIV.

Burkitt lymphoma is associated with the c-myc gene translocation, usually t(8;14). The Epstein-Barr virus (EBV) is strongly implicated in development of the African form of Burkitt lymphoma and to a lesser extent, the sporadic form.

Management of the lymphoma is with chemotherapy. This tends to produce a rapid response which may cause TLS.

The patient has paroxysmal nocturnal haemoglobinuria (PNH). The classic sign of the disease is red discolouration of the urine due to the presence of haemoglobin and hemosiderin from the breakdown of red blood cells. As the urine is more concentrated in the morning, this is when the colour is most pronounced.

PNH is an acquired clonal disorder of haematopoietic stem cells, characterised by variable combinations of intravascular haemolysis, thrombosis, and bone marrow failure. Diagnosis is made by flow cytometric evaluation of blood, which confirms the CD55 and CD59 deficiencies and deficiency of expression of other GPI-linked proteins. This test is replacing older complement-based assays such as the Ham test and sucrose lysis test.

Good prognosis of chronic lymphocytic leukaemia (CLL) is associated with deletion of the long arm of chromosome 13 (del 13q). This is the most common abnormality, seen in around 50% of all CLL patients. Poor prognosis of the disease is related to deletion of part of the short arm of chromosome 17 (del 17p). This is seen in around 5-10% of the patients suffering from CLL.

Poor prognostic factors of CLL include:
1. Male sex
2. Age >70 years
3. Lymphocyte count >50
4. Prolymphocytes comprising more than 10% of blood lymphocytes
5. Lymphocyte doubling time <12 months
6. Raised LDH
7. CD38 expression positive

CXR, blood, and urine tests should be carried out initially to exclude an underlying malignancy. If these are normal, a CT scan of abdomen and pelvis should be arranged as the patient’s age is >40 years. Antiphospholipid antibodies should also be checked for the first unprovoked DVT/PE. There is no history, however, to support an inherited thrombophilia.

The National Institute for Health and Care Excellence (NICE) published guidelines in 2012 for the investigation and management of DVT. If a patient is suspected of having DVT, a two-level DVT Wells score should be used:

DVT likely: 2 points or more
DVT unlikely: 1 point or less

This system of points is based on the following clinical features:
1. Active cancer (treatment ongoing, within six months, or palliative)—1
2. Paralysis, paresis, or recent plaster immobilisation of the lower extremities—1
3. Recently bedridden for three days or more, or major surgery within 12 weeks requiring general or regional anaesthesia—1
4. Localised tenderness along the distribution of the deep venous system—1
5. Entire leg swollen—1
6. Calf swelling at least three cms larger than the asymptomatic side—1
7. Pitting oedema confined to the symptomatic leg—1
8. Collateral superficial veins (non-varicose)—1
9. Previously documented DVT—1
10. An alternative diagnosis is at least as likely as DVT—2

If two points or more—DVT is ‘likely’
If one point or less—DVT is ‘unlikely’

Management

1. LMWH or fondaparinux should be given initially after a DVT is diagnosed.
2. A vitamin K antagonist such as warfarin should be given within 24 hours of the diagnosis.
3. LMWH or fondaparinux should be continued for at least five days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range.
4. Warfarin should be continued for at least three months. At three months, clinicians should assess the risks and benefits of extending the treatment.
5. Consider extending warfarin beyond three months for patients with unprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding. This essentially means that if there is no obvious cause or provoking factor (surgery, trauma, significant immobility, etc.), it may be implied that the patient has a tendency to thrombose and should be given treatment longer than the normal of three months. In practice, most clinicians give six months of warfarin for patients with an unprovoked DVT/PE.
6. For patients with active cancer, LMWH should be used for six months.

As both malignancy and thrombophilia are obvious risk factors for DVT, therefore, all patients with unprovoked DVT/PE who are not already known to have cancer should undergo the following investigations:
1. Physical examination (guided by the patient’s full history)
2. Chest X-ray
3. Blood tests (full blood count, serum calcium, and liver function tests) and urinalysis
4. Testing for antiphospholipid antibodies
5. Testing for hereditary thrombophilia in patients who have had unprovoked DVT/PE and have a first-degree relative who has a history of DVT/PE.

Gram-staining of the blood cultures of this patient will show gram-positive cocci. Gram-negative bacilli used to be the most common pathogen isolated in neutropenic sepsis, but currently, the most common pathogens are gram-positive organisms. Staphylococcus epidermidis is the most frequent causative agent, and following this are other staphylococci and streptococci species.

Neutropenic sepsis is a relatively common complication of cancer therapy—usually chemotherapy. It most commonly occurs 7-14 days after the treatment and is usually defined as a neutrophil count of <0.5 x 10^9/L in a patient undergoing anticancer treatment and who has either a temperature higher than 38°C or has other features consistent with clinically significant sepsis. Management approach includes starting empirical antibiotic therapy (piperacillin with tazobactam—Tazocin) immediately. Following this initial treatment, the patient is usually assessed by a specialist and risk-stratified to see if outpatient treatment may be possible. However, if the patient remains febrile and unwell after 48 hours, an alternative antibiotic such as meropenem is often prescribed with or without vancomycin. If patient is still not responding after 4-6 days, then an antifungal, such as amphotericin B, is started after carrying out investigations (e.g. HRCT and Aspergillus PCR) to determine the likelihood of systemic fungal infection.

Out of the aforementioned markers, low corrected calcium is the only biochemistry result consistent with the diagnosis. All of the other markers are elevated in TLS.

TLS is a potentially fatal condition occurring as a complication during the treatment of high-grade lymphomas and leukaemias. It occurs from the simultaneous breakdown (lysis) of the tumour cells and subsequent release of chemicals into the bloodstream. This leads to hyperkalaemia and hyperphosphatemia in the presence of hyponatraemia. As phosphate precipitates calcium, the serum concentration of calcium becomes low. TLS can occur in the absence of chemotherapy, but it is usually triggered by the introduction of combination chemotherapy. Awareness of the condition is critical for its prophylactic management.

Patients at high risk of TLS should be given IV rasburicase or IV allopurinol immediately prior to and during the first few days of chemotherapy. Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water soluble than uric acid and is therefore more easily excreted by the kidneys. Patients in lower-risk groups
should be given oral allopurinol during cycles of chemotherapy in an attempt to avoid the condition.

TLS is graded according to the Cairo-Bishop scoring system as:
1. Laboratory tumour lysis syndrome
2. Clinical tumour lysis syndrome

Tumour marker CA 125 is mostly associated with primary peritoneal cancer and ovarian cancer. It can be used to monitor response to chemotherapy, alongside regular CT scans.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

Tumour marker CA 15-3 is mostly associated with breast cancer.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

There are two main reasons for using combinations of chemotherapeutic agents rather than single agents. First, different drugs exert their effects through different mechanisms, therefore, carefully combining them will increase the number of tumour cells killed in each cycle as well as decrease their chances of developing drug resistance. Second, there may be an even greater effect with drugs that are synergistic.

An MRI whole spine should be performed in a patient suspected of spinal metastasis which can occur before developing metastatic spinal cord compression. This patient has renal cell carcinoma, which readily metastasises to the bones and also has progressive back pain. He, therefore, needs urgent imaging of his spine before any neurological compromise develops. MRI whole spine is preferable because patients with spinal metastasis often have metastases at multiple levels within the spine. Plain radiographs and CT scans should not be performed as they have a lower sensitivity for revealing lesions and cannot exclude cord compression.

In general, imaging should be performed within one week if symptoms suspicious of spinal metastasis without neurological symptoms are present. If there are symptoms suggestive of malignant spinal cord compression, then imaging should be done within 24 hours.

The signs and symptoms of spinal metastases include:
1. Unrelenting lumbar back pain
2. Thoracic or cervical back pain
3. Pain associated with tenderness and worsens with sneezing, coughing, or straining
4. Nocturnal pain

Extra-nodal presentation is more common in non-Hodgkin lymphoma (NHL) than in Hodgkin lymphoma (HL). Bone marrow infiltration is more common in low-grade than in high-grade NHLs.

Low-grade NHL is predominantly a disease of older people. Most present with advanced disease, bone marrow infiltration being almost invariable. Anaemia, leucocytosis, and/or thrombocytopaenia in a patient are suggestive of bone marrow involvement. For definitive diagnosis, lymph node biopsy is sufficient.

The other aforementioned statements are ruled out because:
1. Renal impairment in NHL usually occurs as a consequence of ureteric obstruction secondary to intra-abdominal or pelvic lymph node enlargement.

2. Burkitt lymphoma is a high-grade NHL, which was first described in children in West Africa who presented with a jaw tumour, extra-nodal abdominal involvement, and ovarian tumours. It develops most often in children or young adults and is uncommon in older people.

3. High-grade lymphomas are potentially curable. They have a better prognosis and are responsive to chemotherapy unlike low-grade lymphomas, which are incurable with conventional therapy.

Bombesin is a tumour marker elevated in small cell lung carcinomas, as well as in gastric carcinomas and retinoblastomas.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

A translocation between chromosome 15 and 17 is seen in acute promyelocytic leukaemia (APL), which is known to carry a good prognosis.

Acute myeloid leukaemia (AML) is the acute expansion of the myeloid stem line, which may occur as a primary disease or follow the secondary transformation of a myeloproliferative disorder. It is more common over the age of 45 and is characterized by signs and symptoms largely related to bone marrow failure such as anaemia (pallor, lethargy), frequent infections due to neutropenia (although the total leucocyte count may be very high), thrombocytopaenia (bleeding), ostealgia, and splenomegaly. The disease has poor prognosis if:

The disease has poor prognosis if:
1. Age of the patient >60 years
2. >20% blasts seen after the first course of chemotherapy
3. Chromosomal aberration with deletion of part of chromosome 5 or 7.

APL is an aggressive form of AML. It is associated with t(15;17) and has a good prognosis. The general age of presentation is less than that in other types of AML (average age is 25 years old). On blood film, abundant Auer rods are seen with myeloperoxidase staining. Thrombocytopaenia or DIC is seen in patients presenting with this disease.

Lead poisoning is characterised by abdominal pain, fatigue, constipation, peripheral neuropathy (mainly motor), and blue lines on gum margin in 20% of the adult patients (very rare in children).

For diagnosis, the level of lead in blood is usually considered with levels greater than 10 mcg/dL being significant. Furthermore, the blood film shows microcytic anaemia and basophilic stippling of red blood cells. Urinary coproporphyrin is increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased). Raised serum and urine levels of delta-aminolaevulinic acid may also be seen, making it sometimes difficult to differentiate from acute intermittent porphyria.

Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion characterised by the acute onset of non-cardiogenic pulmonary oedema following transfusion of blood products.

TRALI is a more severe manifestation of the febrile non-haemolytic group of transfusion reactions and usually occur in patients who have had multiple previous transfusions. TRALI is related to leucocyte antibodies which are present in the plasma of the blood donor. Multiparous women are the highest-risk donors for TRALI.

For management, leucocyte-depleted blood is now used for transfusion and this is associated with a reduced risk of this type of transfusion reaction.

The patient is displaying signs and symptoms of hyperviscosity syndrome, secondary to the Waldenström’s macroglobulinemia. Treatment of choice is plasmapheresis.

Waldenström’s macroglobulinemia (also called lymphoplasmacytic lymphoma) is an uncommon type of non-Hodgkin lymphoma seen in older people. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein. Its features include monoclonal IgM paraproteinemia; hyperviscosity syndrome leading to bilateral central retinal vein occlusion (CRVO) and hence, visual disturbances; weight loss and lethargy; hepatosplenomegaly and lymphadenopathy; and cryoglobulinemia. It is not, however, associated with bone pain.

Philadelphia translocation, t(9;22), is a marker of poor prognosis in acute lymphoblastic leukaemia (ALL).

ALL is the malignancy of lymphoid progenitor cells affecting B or T cell lineage. This results in the arrest of lymphoid cell maturation and proliferation of immature blast cells (lymphoblasts), leading to bone marrow and tissue infiltration.

ALL is the most common type of childhood cancers. Its peak incidence is between two to three years of age.

Acute B lymphoblastic leukaemia (B-ALL) is the most common type of ALL, involving overproduction of B-cell lymphoblasts. It is manifested by low initial WCC and is associated with a good prognosis.

Poor prognostic factors for ALL include:
1. Pre-B cell or T-cell ALL (T-ALL)
2. Philadelphia translocation, t(9;22)
3. Age <2 years or >10 years
4. Male sex
5. CNS involvement
6. High initial WBC (e.g. >100 x 10^9/L)
7. non-Caucasian

The patient is asymptomatic but matches the diagnostic criteria for multiple myeloma (MM). Therefore, the underlying diagnosis of this condition is smouldering multiple myeloma (SMM). SMM is an early precursor to MM. Its treatment is typically to watch and wait.

MM is a neoplasm of the bone marrow plasma cells. Peak incidence is in patients aged 60–70 years.

Clinical features of MM include:
1. Ostealgia, osteoporosis, pathological fractures (typically vertebral), and osteolytic lesions
2. Lethargy
3. Infections
4. Hypercalcaemia
5. Renal failure
6. Other features: amyloidosis e.g. macroglossia, carpal tunnel syndrome; neuropathy; hyperviscosity

Diagnosis of MM is based on the confirmation of (a) one major criterion and one minor criterion or (b) three minor criteria in an individual who has signs or symptoms of multiple myeloma.

Major criteria:
1. >30% plasma cells on bone marrow biopsy
2. Monoclonal band of paraprotein on electrophoresis: >35g/L for IgG, 20g/L for IgA, or >1g of light chains excreted in the urine per day

Minor criteria:
1. 10–30% plasma cells on bone marrow biopsy
2. Abnormal monoclonal band but levels less than listed above
3. Lytic bone lesions observed radiographically
4. Immunosuppression

The major delayed problem with radiotherapy is the development of secondary cancers. This risk begins to appear ten years after therapy.

5–15% of the cases of polycythaemia vera progress to myelofibrosis or acute myeloid leukaemia (AML).

Polycythaemia vera (PV), also known as polycythaemia rubra vera, is a myeloproliferative disorder caused by clonal proliferation of marrow stem cells leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has peak incidence in the sixth decade of life, with typical features including hyperviscosity, pruritus, splenomegaly, haemorrhage (secondary to abnormal platelet function), and plethoric appearance.

Some management options of PV include lose-dose aspirin, venesection (first-line treatment), hydroxyurea (slightly increased risk of secondary leukaemia), and radioactive phosphorus (P-32) therapy.

In PV, thrombotic events are a significant cause of morbidity and mortality. 5–15% of the cases progress to myelofibrosis or AML. The risk of having AML is increased with chemotherapy treatment.

The diagnosis for the aforementioned case is thrombotic thrombocytopenic purpura (TTP). TTP is classically characterised as a pentad of thrombocytopaenia, microvascular haemolysis, fluctuating neurological signs, renal impairment, and fever.

The differential diagnosis for severe thrombocytopaenia is immune thrombocytopenic purpura (ITP). ITP is more common than TTP. However, a patient of ITP would not present with the range of symptoms seen in this scenario.

In TTP, there is deficiency of a protease which breaks down large multimers of von Willebrand factor. This leads to abnormally large and sticky multimers of von Willebrand factor which cause platelets to clump within the vessels.

Untreated TTP has a mortality rate of up to 90%. Therefore, rapid plasma exchange (PEX) may be a life-saving intervention. Platelet transfusion in TTP is only indicated if there is an ongoing life-threatening bleed. Intravenous methylprednisolone is indicated after treatment with PEX has been completed. There is no current role of intravenous immunoglobulin in the routine management of TTP. However, there have been reports of its successful use in PEX- and steroid-refractory cases. Intravenous argatroban is indicated in heparin-induced thrombocytopaenia (HIT), but there is no history of recent heparin administration or hospitalisation in this patient nor are the clinical signs consistent with HIT.

Management options for TTP include PEX as the treatment of choice. Steroids and immunosuppressants are also given. Antibiotics are not recommended as they may worsen the outcome of the disease. For cases resistant to PEX and pharmacologic therapy, vincristine is given.

The direct Coombs test will specifically confirm immune-mediated haemolysis occurring post-transfusion in the aforementioned case.

There are two types of Coombs test used in immunohematology and immunology:

1. Direct Coombs test—It confirms autoimmune haemolytic anaemia by detecting antibodies or complement proteins attached to the surface of red blood cells.

2. Indirect Coombs test—It is used in prenatal testing of pregnant women and in testing prior to a blood transfusion. It detects antibodies floating freely in the blood, against foreign red blood cells.

This is a classical picture of graft versus host disease (GVHD) following bone marrow transplant. Acute GVHD occurs in the first 100 days post transplant with chronic GVHD occurring 100-300 days after transplant. GVHD is graded according to the Seattle system, and each organ involved is scored (skin, liver, and gut).

The standard initial treatment in the acute setting is high-dose methylprednisolone started immediately. If there is no response, a more intensive immunosuppressive agent such as alemtuzumab or antilymphocyte globulin is needed.

Leukemoid reaction has a high LAP score.

Leukemoid reaction refers to leucocytosis occurring as a physiological response to stress or infection which may be mistaken for leukaemia, especially chronic myeloid leukaemia (CML). Leucocytosis occurs, initially, because of accelerated release of cells from the bone marrow and is associated with increased count of more immature neutrophils in the blood (left-shift). In order to differentiate, LAP score is used. Leukocytic alkaline phosphatase (ALP) activity is high in a leukemoid reaction but low in CML.

LAP score is high in:
1. Leukemoid reaction
2. Infections
3. Myelofibrosis
4. Polycythaemia rubra vera
5. Steroids, Cushing’s syndrome
6. Pregnancy, oral contraceptive pill

LAP score is low in:
1. CML
2. Pernicious anaemia
3. Paroxysmal nocturnal haemoglobinuria (PNH)
4. Infectious mononucleosis