Other Blood Disorders: Platelets, White Cells, Polycythaemia and Coagulation

Other Blood Disorders: White-Cell, Platelet, Red-Cell Excess, Marrow and Coagulation Disorders

Study level: Clinical medicine, emergency medicine and pathology | Topic: Hematology

Learning objectives

• Classify leukocyte, platelet, erythrocyte and coagulation abnormalities.
• Distinguish reactive changes from clonal marrow disease.
• Recognise thrombocytopenia, thrombocytosis, neutropenia, leukocytosis and polycythaemia.
• Explain common bleeding disorders, disseminated intravascular coagulation and thrombophilia.
• Recognise haematologic emergencies and select first investigations.

1. A pattern-based approach

Pattern	First questions	Urgent danger
One abnormal cell line	Is the change reactive, drug-related, immune, nutritional or clonal?	Severe neutropenia, critical thrombocytopenia, symptomatic polycythaemia.
Two or three cytopenias	Marrow failure/infiltration, hypersplenism, infection, drug or nutritional deficiency?	Sepsis, haemorrhage, acute leukaemia.
High counts	Dehydration/stress/infection versus myeloproliferative neoplasm.	Leukostasis, thrombosis, hyperviscosity.
Bleeding	Platelet-type mucosal bleeding or coagulation-factor deep bleeding?	Intracranial, airway, retroperitoneal or obstetric bleeding.
Thrombosis	Provoked versus unprovoked; arterial versus venous; malignancy or antiphospholipid syndrome?	Stroke, pulmonary embolism, limb or mesenteric ischemia.

2. White-cell disorders

2.1 Leukocytosis

Leukocytosis is an age-adjusted increase in total WBC count. Identify the lineage and look at the smear before assuming infection.

Pattern	Common reactive causes	Clonal/other causes
Neutrophilia	Bacterial infection, inflammation, stress, smoking, corticosteroids, tissue necrosis.	Chronic myeloid leukaemia, other myeloproliferative neoplasms, severe leukemia.
Lymphocytosis	Viral infection, pertussis, recovery from infection.	Chronic lymphocytic leukaemia, lymphoproliferative disorders.
Eosinophilia	Helminths, allergy, asthma, drug reaction.	Clonal eosinophilic neoplasm, Hodgkin lymphoma, selected solid tumours.
Monocytosis	Chronic infection, inflammatory disease, recovery from neutropenia.	Chronic myelomonocytic leukaemia.
Basophilia	Allergy/inflammation, rarely reactive alone.	Strong clue to myeloproliferative neoplasm, especially CML.

2.2 Leukopenia and neutropenia

Causes include viral infection, sepsis, drugs (especially chemotherapy, antithyroid agents and some antibiotics), autoimmune disease, nutritional deficiency, marrow failure and hypersplenism. Calculate the ANC; severity and duration determine infection risk.

• Mild neutropenia: may be transient; review trend and cause.
• Severe/prolonged neutropenia: fever is an emergency even without localising signs.
• Examination: inspect mouth, skin, perianal area, lungs, catheter sites and abdomen; avoid unnecessary rectal examination in profound neutropenia.
• Investigations: repeat CBC/film, cultures, medication review, viral testing, B12/folate/copper, autoimmune tests and marrow examination when persistent.

3. Platelet disorders

3.1 Thrombocytopenia

Platelets below the laboratory reference threshold (often <150 × 10⁹/L) may reflect decreased production, increased destruction/consumption, sequestration or dilution.

Mechanism	Examples	Clues
Pseudothrombocytopenia	EDTA-dependent platelet clumping.	Unexpected isolated low count; clumps on film; repeat in citrate.
Reduced production	Marrow failure, leukemia, chemotherapy, alcohol, B12/folate deficiency, viral disease.	Other cytopenias, abnormal film or low reticulocytes.
Immune destruction	ITP, drug-induced thrombocytopenia, HIV, SLE, post-transfusion.	Often isolated thrombocytopenia; large young platelets.
Consumption	DIC, TTP/HUS, severe sepsis, HELLP, massive haemorrhage.	Schistocytes, organ injury, abnormal coagulation in DIC.
Sequestration/dilution	Hypersplenism, liver disease, massive transfusion/fluids.	Splenomegaly or dilution context.

Platelet-type bleeding produces petechiae, purpura, epistaxis, gum bleeding and menorrhagia. Deep muscle/joint bleeding is more typical of coagulation-factor deficiency. Always ask about antiplatelet drugs, anticoagulants and herbal products.

3.2 Thrombocytosis

Reactive thrombocytosis follows infection, inflammation, iron deficiency, surgery, trauma or splenectomy. Clonal thrombocytosis (essential thrombocythaemia) is a myeloproliferative neoplasm; JAK2, CALR or MPL mutations may be present. Very high counts can paradoxically cause bleeding through acquired von Willebrand dysfunction while also increasing thrombosis risk.

4. Polycythaemia (erythrocytosis)

Polycythaemia is an increased red-cell mass; a high Hb/Hct may also reflect reduced plasma volume (relative erythrocytosis).

Type	Causes	Clues/tests
Relative	Dehydration, diuretics, stress erythrocytosis.	Volume depletion; correct hydration and repeat.
Secondary appropriate	Chronic hypoxia from lung disease, cyanotic heart disease, sleep apnoea or high altitude.	Low oxygen saturation, smoking/carboxyhaemoglobin; EPO usually high.
Secondary inappropriate	Renal/hepatic tumours, exogenous EPO or androgen use.	High EPO without hypoxia; image when indicated.
Primary/clonal	Polycythaemia vera, usually JAK2-driven myeloproliferative neoplasm.	Low EPO, leukocytosis/thrombocytosis, splenomegaly, aquagenic pruritus, erythromelalgia.

Hyperviscosity causes headache, visual symptoms, dizziness, hypertension and thrombosis. Sudden neurologic deficit, chest pain, limb ischemia or abdominal pain is an emergency.

5. Marrow and blood cancers

5.1 Leukaemia

Leukaemia is malignant proliferation of haematopoietic precursors. Acute disease has blasts and rapid marrow failure; chronic disease may be indolent but can transform.

• Acute leukaemia: fatigue/pallor, infection, bruising/bleeding, bone pain, lymphadenopathy, hepatosplenomegaly and blasts.
• CML: marked leukocytosis with left shift, basophilia and splenomegaly; BCR-ABL1 testing confirms.
• CLL: persistent clonal B lymphocytosis, lymphadenopathy, recurrent infection and autoimmune cytopenias.
• Investigations: urgent CBC/film, flow cytometry, marrow aspirate/biopsy, cytogenetics and molecular testing.

5.2 Lymphoma and plasma-cell disorders

Lymphomas present with persistent lymphadenopathy, B symptoms (fever, drenching night sweats, weight loss), extranodal masses or cytopenias. Myeloma causes bone pain/lytic lesions, renal impairment, hypercalcaemia and anaemia; serum/urine electrophoresis, free light chains and marrow testing are used.

6. Coagulation and bleeding disorders

6.1 Primary versus secondary haemostasis

Defect	Typical bleeding	Examples
Platelet/vWF (primary)	Mucosal bleeding, petechiae, immediate bleeding after injury, menorrhagia.	ITP, aspirin effect, von Willebrand disease.
Coagulation factors (secondary)	Deep muscle/joint bleeding, delayed post-procedure bleeding, large haematomas.	Haemophilia A/B, vitamin K deficiency, liver disease.
Mixed consumption	Bleeding and thrombosis together.	DIC, severe liver failure, TTP/HUS.

6.2 Screening tests

• PT/INR: extrinsic/common pathways; prolonged in warfarin effect, vitamin K deficiency, liver disease and factor VII deficiency.
• aPTT: intrinsic/common pathways; prolonged in haemophilia, heparin effect, lupus anticoagulant and some inhibitors.
• Fibrinogen and D-dimer: consumption/fibrinolysis pattern; D-dimer is sensitive but nonspecific.
• Platelet count and film: thrombocytopenia, clumping or schistocytes.
• Mixing study and factor assays: distinguish factor deficiency from inhibitors when PT/aPTT is prolonged.

6.3 High-yield disorders

• Von Willebrand disease: inherited quantitative/qualitative vWF defect; mucosal bleeding and menorrhagia; check vWF antigen/activity and factor VIII.
• Haemophilia A/B: X-linked factor VIII/IX deficiency; recurrent haemarthroses and deep bleeding. CDC guidance emphasises factor replacement, with prophylaxis for many patients.
• Vitamin K deficiency/antagonism: prolonged PT first; causes include malabsorption, antibiotics, liver disease and warfarin.
• Liver failure: reduced clotting-factor production, thrombocytopenia and altered anticoagulants; INR alone does not perfectly predict bleeding.
• DIC: systemic thrombin generation consumes platelets and factors, causing simultaneous microvascular thrombosis and bleeding.
• Thrombophilia: inherited or acquired tendency to thrombosis, including antiphospholipid syndrome, factor V Leiden and malignancy-associated clotting.

7. Haematologic emergencies

Emergency	Recognition	Immediate priorities
Febrile neutropenia	Fever/hypothermia plus severe neutropenia.	Sepsis pathway, cultures and immediate empiric antimicrobials; do not delay for imaging.
Major thrombocytopenic bleeding	Intracranial, airway, GI, retroperitoneal or uncontrolled mucosal bleeding.	ABCDE, direct pressure, urgent haematology/transfusion support and cause-specific therapy.
TTP/HUS	Thrombocytopenia, schistocytes, haemolysis, renal or neurologic injury.	Urgent plasma-exchange pathway for suspected TTP; do not wait for ADAMTS13.
DIC	Bleeding/thrombosis with prolonged PT/aPTT, low fibrinogen, high D-dimer and severe trigger.	Treat sepsis/obstetric/trauma/malignancy cause and support organs/coagulation.
Leukostasis	Very high WBC with dyspnoea, hypoxia, confusion, headache or focal neurologic deficits.	ICU/haematology urgently; manage oxygenation, leukoreduction and tumour lysis risk.
Hyperviscosity	Visual change, headache, mucosal bleeding, neurologic symptoms, dyspnoea or confusion.	Urgent specialist therapy, hydration tailored to status and treatment of the underlying clone.
Major haemophilia bleed	Head injury/headache, neck/throat swelling, iliopsoas or joint bleeding.	Give prescribed factor replacement immediately and image/consult; do not wait for laboratory confirmation.

8. Diagnostic workflow

1. Repeat an unexpected result and inspect the film for clumping, blasts or schistocytes.
2. Ask about bleeding/thrombosis phenotype, infection, weight loss, night sweats, medications, pregnancy, travel, transfusion and family history.
3. Examine skin, mucosa, lymph nodes, spleen, liver, joints and neurologic status.
4. Order CBC/differential, film, reticulocytes, PT/INR, aPTT, fibrinogen, D-dimer, renal/liver tests and targeted tests.
5. Escalate to flow cytometry, marrow, molecular tests, factor assays, vWF studies, JAK2/BCR-ABL1 or imaging according to pattern.

9. Treatment principles

• Treat the cause: infection/inflammation, iron deficiency, malignancy, medication effect, liver disease or nutritional deficiency.
• In bleeding, use local control, pressure, antifibrinolytic or factor/platelet support only according to the diagnosis and local protocol.
• In thrombosis, anticoagulate when safe and investigate provoking factors; balance bleeding risk and platelet count.
• For clonal marrow disease, specialist-directed cytoreduction, targeted therapy, chemotherapy or transplantation may be required.
• Avoid intramuscular injections, aspirin/NSAIDs and invasive procedures in severe thrombocytopenia or haemophilia unless explicitly indicated.
• Reassess trends rather than reacting to one number; treatment can change counts and mask disease.

10. Clinical cases

Case 1: isolated low platelets

A well patient has a platelet count of 18 × 10⁹/L, normal Hb/WBC and no splenomegaly. Repeat the sample in citrate and inspect the film to exclude clumping, then assess for ITP, drugs, HIV/hepatitis and bleeding. New severe headache, neurologic signs or GI bleeding changes the urgency completely.

Case 2: erythrocytosis with headache

A smoker with high Hb has headache and pruritus. Check oxygenation/carboxyhaemoglobin, hydration, EPO and JAK2, and assess for sleep apnoea or renal disease. Visual loss, focal neurologic deficit or chest pain suggests acute hyperviscosity/thrombosis.

Case 3: prolonged aPTT and joint swelling

A boy with recurrent knee swelling has isolated prolonged aPTT and a family history of maternal male relatives with bleeding. Suspect haemophilia; send factor VIII/IX assays and give urgent factor replacement for significant bleeding or head injury.

11. Quick self-test

1. What causes a neutrophilia besides bacterial infection?
2. How do platelet-type and coagulation-factor bleeding differ clinically?
3. List three causes of thrombocytopenia due to consumption.
4. What is the danger of schistocytes with thrombocytopenia?
5. What tests screen the intrinsic and extrinsic coagulation pathways?
6. What symptoms suggest leukostasis?

Answers

1. Stress, corticosteroids, smoking, tissue necrosis, inflammation and myeloproliferative disease.
2. Platelet/vWF bleeding is mucosal and immediate; factor deficiency produces deep muscle/joint and delayed post-procedure bleeding.
3. DIC, TTP/HUS, severe sepsis and HELLP syndrome.
4. Microangiopathic haemolysis such as TTP, HUS or DIC, which may be rapidly fatal without urgent treatment.
5. PT/INR mainly assesses extrinsic/common pathways; aPTT assesses intrinsic/common pathways.
6. Dyspnoea/hypoxia, headache, confusion, visual symptoms, focal neurologic deficits or priapism in extreme leukocytosis.

Key take-home points

• Always confirm abnormal counts, review the film and identify the affected cell line.
• Reactive and clonal disorders can look similar; persistence, severity, blasts, basophilia and organomegaly increase concern for marrow disease.
• Thrombocytopenia causes mucosal bleeding; factor disorders cause deep bleeding; DIC causes both bleeding and thrombosis.
• Neutropenic fever, TTP, DIC, leukostasis, hyperviscosity and intracranial haemorrhage are time-critical emergencies.
• Do not give empiric iron or platelets without establishing the pattern and cause; treatment can be harmful when misdirected.

Selected references

• MedlinePlus: Blood Disorders
• NCBI Bookshelf: Thrombocytopenia
• NCBI Bookshelf: Leukocytosis
• NCBI Bookshelf: Polycythemia
• CDC: About Hemophilia
• CDC: Diagnosing Hemophilia