Abnormal blood count

Question 1

Balance in haemostasis examples

Answer 1

-Accumulation
=Low Clearance
(Hyposplenism)
=High production (inflammation, drugs, proliferative malignancy)

-Depletion
=High clearance (hypersplenism, immune destruction)
=Low production (marrow failure, drugs)

Question 2

Balance in neutrophils

Answer 2

-Accumulation
=Steroids (marrow overproduce cells)
=Infection
=Inflammation
=CML (chronic myeloid leukaemia)

-Depletion
=ACUTE INFECTION
=Tissue Homing- transient neutropenia
=Immune- SLE, Marrow failure
=Drugs- cytotoxics, idiosyncratic

Question 3

Balance in platelets

Answer 3

-Accumulation
=Infection and inflammation
=Iron deficiency
=Myeloproliferative disorders

-Depletion
=Drugs- cytotoxic, quinine
=Bleeding and DIC
=Immune (ITP)
=Microangiopathy
=Marrow Failure

Question 4

Balance in lymphocytes

Answer 4

-Accumulation
=Viral infection
=Inflammation
=Lymphoid malignancy

-Depletion
=Viral infection (HIV?)
=Drugs- cytotoxic
=Ageing
=Marrow Failure

Question 5

What is polycythaemia?

Answer 5

-Abnormal accumulation of red blood cells

-Haematocrit: proportion of red cells
-Haemoglobin: concentration (g/L)

-Normal: little under half
-Relative: (plasma volume reduced)
-True: excess production (marrow disorder)

Question 6

Causes of relative polycythaemia

Answer 6

-Dehydration
-Diuretics

Question 7

Causes of True polycythaemia

Answer 7

-Erythropoietin
-Androgens
-Malignancy- polycythaemia vera

Question 8

What suggests infection?

Answer 8

-Generalised Leucocytosis
-Thrombocytosis
=Infection
=Acute phase response

Question 9

Causes of eosinophilia

Answer 9

-Neoplastic
-Allergic
-Autoimmune
-Parasites

Question 10

Full blood count in liver disease

Answer 10

-Macrocytosis (lipid change in red cell membrane)
-Splenomegaly (portal hypertension)= hypersplenism= neutropenia and thrombocytopenia
-Not making thrombopoietin (marrow suppression) so thrombocytopenia

Question 11

Precipitants of encephalopathy

Answer 11

-Infection
-GI bleeding
-Protein meal

Question 12

Presentation of thrombocytopenia

Answer 12

Ask about recent or current symptoms of bleeding, which are commonly epistaxis or easy bruising with minor trauma. Haematuria and gastrointestinal bleeding are unusual, but menorrhagia can be a common symptom. In general, a platelet count above 30×109/L is unlikely to cause bleeding unless abnormal platelet function exists in the form of antiplatelet agents or myelodysplasia. Substantial bleeding tends to happen only if the count drops much below 20×109/L. Spontaneous intracranial haemorrhage secondary to thrombocytopenia usually occurs only with platelet counts less than 10×109/L. Further questions may be directed to identifying the possible causes of thrombocytopenia

Question 13

Risk factors/ pointer to thrombocytopenia diagnosis

Answer 13

-Recent viral infections (glandular fever): common young adults
-Drugs: H2 blockers, paroxetine, furosemide. metronidazole
-Herbal remedies
-Immune thrombocytopenia in young women of reproductive age: autoimmune disease like thyroid, SLE, pernicious anaemia. Tiredness
-Chronic liver disease (cirrhosis), alcohol
-Hep C HIV
-Helicobacter pylori

Question 14

History and examination of thrombocytopenia

Answer 14

-Signs of bruising
-History of bleeding; epistaxis, gum bleeds, melena
-Stop aspirin and warfarin

Question 15

Causes of thrombocytosis

Answer 15

The differential diagnosis for thrombocytosis is broad (table)and the diagnostic process can be challenging.7 Rarely, non-platelet structures in peripheral blood can be erroneously counted as “platelets” in automated FBC counters, leading to a spurious thrombocytosis.8 The two main classes of genuine thrombocytosis are secondary or reactive causes and primary or clonal causes (ie, haematological neoplasms) (box 1). In one cohort study of 732 people with an elevated platelet count, the thrombocytosis in 80-90% of patients was reactive to an underlying inflammatory cause

Question 16

What is reactive thrombocytosis?

Answer 16

proliferation of platelets is caused by a response to growth factors released from an underlying inflammatory or malignant condition, and is not due to a primary haematological disorder. The platelet count should normalise after resolution of the acute disease state

Reactive thrombocytoses are driven by thrombopoietic growthfactors released in response to acute blood loss, iron deficiency,haemolysis, malignancy, infections, and acute or chronicinflammatory states, notably rheumatological conditions ortissue damage.1 These factors, including thrombopoietin,regulate the differentiation and proliferation of the platelet“parent” cell, the megakaryocyte.A large prospective cohort study6 highlights the diagnosticimportance of an incidental finding of thrombocytosis in generalpractice. The 12 month incidence of all cancers was higher inpatients with thrombocytosis (11.6% in men, 6.2% in women)than in those without (4.1% in men, 2.2% in women).Paraneoplastic thrombocytosis is a poor prognostic feature inmany solid tumours

Question 17

What is clonal thrombocytosis?

Answer 17

caused by underlying myeloproliferative or myelodysplastic neoplasm. A growing number of acquired “driver” mutations causing autonomous proliferation through aberrantly activated cellular signalling pathways have been identified, most commonly JAK2V617F

Clonal thrombocytosis arises from an expansion of a mutatedhaematopoietic stem cell or myeloid progenitor cells, whichgive rise to megakaryocytes.11 It is most characteristic ofessential thrombocythaemia but is also seen in othermyeloproliferative neoplasms (MPNs) such as polycythaemiavera, primary myelofibrosis, and chronic myeloid leukaemia,nd in some myelodysplastic syndromes. Diagnostic criteriaexist for MPNs12 and they should be managed in conjunctionwith a haematologist or other specialist experienced in treatingthese conditions. Essential thrombocythaemia is associated witha relatively high risk of thrombotic complications, such as strokeand venous thromboembolism.13 Risk scores based on patientand disease factors can help guide decisions on the use ofprophylactic antiplatelet agents or cytoreductive therapies toreduce platelet counts

Question 18

History and examination of thrombocytosis

Answer 18

-Most common reactive causes of thrombocytosis: underlying infection, chronic disease, malignancy, anaemia, previous splenectomy, or recent surgery

-Most patients with clonal thrombocytosis are asymptomatic, but some experience vasomotor symptoms (headaches, visual changes, atypical chest pains, or distal limb pain), bleeding complications (due to acquired von Willebrand factor disease), and thrombotic complications.

-Constitutional symptoms such as fatigue and pruritus are common in myeloproliferative disorders and can substantially impair quality of life.

-Hepatosplenomegaly suggests a primary blood disorder. No clear correlation exists between symptoms and platelet counts: while control of the underlying MPN generally leads to the disappearance of vasomotor symptoms, patients with platelet counts>1000×109/L due to reactive thrombocytoses are usually asymptomatic. Symptoms thus likely reflect underlying qualitative platelet abnormalities seen in MPNs

Question 19

Investigations of thrombocytosis

Answer 19

-Peripheral blood smear
-Acute phase reactants (inflammatory markers reactive)
-Iron status (IDA)
-Repeat FBC (persistence/ resolution)
-Cancer investigations
=patients ≥40 with thrombocytosis should be considered for a chest radiograph within two weeks (lung cancer), and women ≥55 with thrombocytosis and unexplained vaginal discharge or macroscopic haematuria should be considered for a pelvic ultrasound (endometrial cancer)
-Haematological investigations may include molecular testing for known driver mutations (such as JAK2 V617F, MPL,BCR-ABL, and CALR mutations) and often cytogenetics and bone marrow aspirate and trephine

Question 20

What is neutropenia defined as?

Answer 20

Neutropenia is defined as an absolute neutrophil count of less than 1.5×109/L. It is important for two reasons. Firstly, it may indicate an underlying systemic or haematological disease. Secondly, it reflects an increased risk of life threatening bacterial infection—risk increases once the count is less than 1.0×109/Land becomes even greater in severe neutropenia

Question 21

Neutropenia investigation

Answer 21

-Review drugs
-Blood film (T cells viral, infective mononucleosis, cytomegalovirus, toxoplasmosis/ autoimmune or reactive conditions)
-Chronic viral serology (HIV, Hep C and B)
-Antinuclear antibodies (SLE)
-Rheumatoid factor
-Antineutrophil antibodies