MSE-2015 L7 Case 6 3 Year Old Orphan

Case Summary

  • Patient Profile: A 3-year-old boy in a foster family for 3 weeks.

  • Incident: Fell from swings, resulting in a nosebleed lasting several hours.

  • Current Health: Generally well, eating and sleeping normally.

Blood Test Results (Page 2)

Full Blood Count Parameters

  • Red Cell Number: 4.6 (Reference: 4.5-6.5 x10^12 Cells/L)

  • Mean Cell Volume: 81 (Reference: 78-95 fl)

  • Haemoglobin: 132 (Reference: Males 130-180 g/L, Females 115-165 g/L)

  • White Cell Count: 4.8 (Reference: 4.00 - 11.00x10^9 Cells/L)

    • Neutrophils: 2.5 (Reference: 2.0 - 7.5 x10^9 Cells/L)

    • Lymphocytes: 1.3 (Reference: 1.0 - 4.5 x10^9 Cells/L)

    • Basophils: 0 (Reference: < 0.1 x10^9 Cells/L)

    • Eosinophils: 0.2 (Reference: 0.04 - 0.40 x10^9 Cells/L)

    • Monocytes: 0.8 (Reference: 0.2 - 0.8 x10^9 Cells/L)

  • Platelets: 165 (Reference: 150-400 x10^9 Cells/L)

Clotting Screen Results

  • Prothrombin Time (PT): 13 (Reference: 11-14 secs)

  • Activated Partial Thromboplastin Time (APTT): 42 (Reference: 24-34 secs)

  • Fibrinogen: 2.1 (Reference: 1.5-4.5 g/L)

Haemophilia A (Page 3)

  • Definition: Caused by deficiency in Factor VIII (FVIII).

  • Genetics: FVIII gene located on the long arm of the X chromosome.

  • Function: Part of the intrinsic tenase complex that activates Factor X.

Epidemiology (Page 4)

  • Occurrence: 1 in 10,000 males.

  • Inheritance: X-linked recessive.

  • Genetic Cause: Most common mutation involves an inversion in the FVIII gene, particularly at intron 22.

Haemophilia A in Females (Page 5)

  • Rarity: Very rare in females.

  • Causes: Documented cases linked to Turner’s Syndrome, homozygosity for FVIII deficiency, and inappropriate lyonization.

Haemophilia B (Page 6)

  • Description: First described in 1952, also known as Christmas disease.

  • Cause: Deficiency in Factor IX (FIX) located on the X chromosome, adjacent to FVIII gene.

  • Inheritance: X-linked recessive disorder.

Clinical Presentation (Page 7)

  • Symptoms: Hemorrhage and advanced haemophilic arthropathy.

  • Radiography: Advanced conditions include loss of cartilage, bone deformities, and irregular joint surfaces.

Coagulation Cascade Impact (Pages 8-10)

Haemophilia A

  • Process: Involves activation of specific factors (e.g., FXII to FXa through intrinsic pathway).

Haemophilia B

  • Process Similarity: FXII leading to FIX activation.

Treatment of Haemophilia A/B (Page 11)

  • Options: Recombinant FVIII/FIX, clotting factor concentrates, cryoprecipitate, Desmopressin, and gene therapy.

Gene Therapy Example (Page 12)

  • Study: AAV5-Factor VIII Gene Transfer in Severe Hemophilia A reporting promising results in gene therapy effectiveness.

Diagnosis Overview (Page 13)

  • Bleeding Assessment: Level of bleeding correlates to anaemia degrees.

  • Clotting Studies: Normal PT; prolonged APTT indicates FVIII/FIX deficiencies.

Measuring Clotting Factors (Page 14)

  • Factor-poor Plasma: Used to assess specific coagulation factors without interference.

  • Test Methods: Patient plasma mixed with factor-poor plasma to observe effects on clotting times.

Patient Evaluation (Page 15)

  • Conclusion: Reflects assessment of hemophilia A diagnosis based on test findings.

Von Willebrand’s Disease Introduction (Page 16)

  • Overview: A heterogeneous disorder resulting in deficiency of von Willebrand Factor (vWF).

  • Prevalence: Approximately 1% in the population.

Function of von Willebrand Factor (Page 17)

  • Role: Essential for binding and protecting inactive FVIII, facilitating interactions with collagen and platelets.

  • Structure: Exists as large multimers in plasma comprised of multiple vWF monomers.

Types of von Willebrand Disease (Page 18)

  • Type 1: Low vWF levels; autosomal dominant.

  • Type 2A/2B: Abnormal multimer assembly; autosomal dominant.

  • Type 2M/2N: Issues with binding; 2M autosomal dominant, 2N autosomal recessive.

  • Type 3: Severe deficiency; autosomal recessive.

Treatment of von Willebrand’s Disease (Page 19)

  • Options: Desmopressin/Vasopressin, cryoprecipitate, recombinant vWF.

Testing for von Willebrand’s Disease (Page 20)

  • Methods: Platelet aggregation assessments; use of ristocetin.

Thromboelastography (Page 21)

  • Function: Tests platelet function and clot strength by measuring reactions to initiators of coagulation.

Reassessment of Patient (Page 22)

  • Results: vWF and FVIII results suggest abnormal clotting feature framing future assessments.

Causes of Spontaneous Bleeding in Children (Page 23)

  • Consideration: Platelet function and quantity abnormalities can present as bleeding issues, though rare compared to coagulation defects.

Platelets Overview (Page 24)

  • Role: Central to hemostasis, forming primary plugs and acting as reservoirs for coagulation factors and calcium.

Thrombopoiesis (Platelet Production) (Page 25)

  • Phases: Includes pre and post-endomitosis influenced by thrombopoietin (TPO).

Platelet Shedding (Thrombocytopoiesis) (Page 26)

  • Characteristics: Governed by TPO, with megakaryocytes producing proplatelet processes reaching capillary systems in the bone marrow.

Introduction to Thrombocytopenia (Page 27)

  • Definition: Reduction in platelet count, with risks increasing markedly under ~20 x10^9 cells/L.

  • Types: Can be either acquired or hereditary conditions.

Laboratory Investigations of Platelets (Page 28)

  • Methods: Range from routine blood counts to specialized tests, noting the importance of recognizing EDTA-mediated clumping.

Pre-analytical Variables Affecting Platelet Function (Page 29)

  • Factors: Include medications (e.g., aspirin), diet influences, supplements, and lifestyle choices (e.g., alcohol, smoking).

Screening Tests for Platelet Function (Page 30)

  • Tests: Bleeding time tests, thromboelastography, and use of platelet function analyzers (PFA-100).

Platelet Function Analysis Techniques (Page 31)

  • Methods: Involves measuring platelet responses to agonists, either using PRP or whole blood methods.

Mechanisms of Platelet Disorders (Page 32)

  • Causes: Can stem from impaired production, increased consumption, or splenic sequestration, alongside functional issues.

Immune Thrombocytopenic Purpura (ITP) (Page 33)

  • Definition: Characterized by low platelet counts and purpuric rash indicating bleeding tendencies.

  • Mechanism: IgG targeting on glycoprotein complexes leads to increased platelet destruction by macrophages.

  • Prognosis: Generally excellent, with many cases spontaneously resolving.

Epidemiology of ITP (Page 34)

  • Prevalence: Approximately 100 cases per million yearly, with juvenile cases presenting acutely.

Haematology in ITP (Page 35)

  • Findings: Low platelet counts alongside potential red cell decreases, otherwise normal haematology unless secondary conditions are present.

Treatment of ITP (Page 36)

  • Management: Involves monitoring rather than proactive coagulant treatment; focus on infection control and stabilizing counts.

Platelet Transfusion Practices (Page 37)

  • Guidelines: Aim to maintain counts above 50 x10^9 cells/L, recognizing the perishability and shelf life of platelet products.