Clinical and Hematological Aspects of Haemophilia: A Comprehensive Review for Diagnostic and Therapeutic Monitoring

By Rahul Eshi1*, Shekhar Vasaikar2, Krishna Patel2, Ramchandra Rathod1

1P.G. College of Pharmaceutical Science and Research, Nandurbar (MS), India
2P G College of Pharmaceutical Sciences and Research, Nandurbar (MS), India

Published: April 2026 | DOI: 10.5281/zenodo.19845130 | Download PDF

Abstract

Haemophilia is a rare X-linked recessive bleeding disorder caused by deficiency of clotting factors VIII or IX. This review highlights clinical manifestations, molecular pathophysiology, diagnostic workflow, and the critical role of laboratory monitoring in haemophilia management. Advanced diagnostic tools such as factor assays, Bethesda assay, and chromogenic assays are essential for accurate diagnosis and monitoring of therapy, including novel treatments such as emicizumab and gene therapy.

Keywords:

Haemophilia A, Factor VIII, coagulation cascade, hemarthrosis, Bethesda assay, chromogenic assay

Introduction

Haemophilia is a genetic bleeding disorder characterized by deficiency of clotting factor VIII (Haemophilia A) or factor IX (Haemophilia B). It is inherited in an X-linked recessive pattern and predominantly affects males. The disease leads to impaired blood coagulation and prolonged bleeding episodes.

Pathophysiology and Molecular Basis

Haemophilia results from mutations in F8 or F9 genes, leading to defective intrinsic coagulation pathway. The absence of factor VIII or IX disrupts thrombin generation, resulting in unstable fibrin clot formation and prolonged bleeding.

Clinical Manifestations and Diagnosis

Clinical severity depends on factor levels. Severe cases present with spontaneous bleeding and hemarthrosis, while mild cases show bleeding after trauma. Diagnosis involves prolonged aPTT with normal PT, followed by factor assays for confirmation. Mixing studies and Bethesda assay are used to detect inhibitors.

Laboratory Monitoring and Treatment

Management involves replacement therapy with clotting factors. Laboratory monitoring includes factor levels, aPTT, and inhibitor detection. The Bethesda assay quantifies inhibitors, while chromogenic assays are used for accurate monitoring in patients receiving novel therapies.

Prevention and Emerging Strategies

Preventive approaches include genetic counseling, prophylactic therapy, and immunotolerance induction. Emerging treatments such as gene therapy and RNA-based therapies offer promising long-term solutions.

Conclusion

Haemophilia management requires integrated clinical and laboratory approaches. Advances in diagnostics and therapy have improved outcomes, but challenges such as inhibitor development and accessibility remain.

References

  1. Srivastava A. Hemophilia guidelines.
  2. Mannucci PM. Hemophilia therapy.
  3. Hoffman M. Coagulation cascade model.
  4. Additional references as per original article.