Bleeding Disorders

Haemostasis

• The normal physiological response preventing significant blood loss after vascular injury.
• Involves the vascular system initiating vasoconstriction.
• Platelet system gets activated, and platelets aggregate to form a plug.
• Activation of the coagulation cascade produces a fibrin plug.

Classification of Bleeding Disorders

• Disorders of blood vessels
• Disorders of platelets
• Disorders of coagulation

Disorders of Blood Vessels

• Can be inherited, such as Connective Tissue Disorders like Ehlers-Danlos Syndrome.
• Hereditary haemorrhagic telangiectasia (HHT) can also cause such disorders
• Can be acquired through severe infections like meningococcal or typhoid.
• Certain drugs like sulphonamides can cause blood vessel disorders
• Vitamin C deficiency and senile purpura are other causes

Disorders of Platelets

• Thrombocytopenia is a platelet disorder.
• Both Idiopathic Thrombocytopenia Purpura (ITP) and liver disease are causes
• Other causes are renal disease, chemotherapy, and radiotherapy.
• Additional causes are Connective Tissue Disorders, rare diseases, and antiplatelet drugs.

Thrombocytopenia

• Defined by a reduced platelet count of below 150 x 10^9/L (normal range is 150-450 x 10^9/L).
• May result from decreased platelet production or failure.
• Can also result from the destruction of circulating platelets.
• Platelet function can also be a factor

Idiopathic Thrombocytopenia Purpura (ITP)

• It is a rare autoimmune disorder.
• The immune system mistakenly targets the body's own platelets.
• Commonly a result of antibody production against platelets.
• Acute ITP arises post-virally, commonly in children after infections like chickenpox and is self-limiting.
• Chronic ITP can occur at any age, and its symptoms may persist from 6 months to a lifetime.

Liver Disease

• The liver is critical for haemostasis, producing coagulation factors I, II, VII, IX, X, and XI.
• Impaired liver function can lead to malabsorption of fat-soluble vitamins like vitamin K.
• Vitamin K is crucial for the synthesis of blood-clotting factors.
• Chronic liver disease prolongs both Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT).
• Post-operative bleeding can occur in alcohol-dependent patients.
• Liver cirrhosis, bone marrow suppression, and folate deficiency are causes
• Heavy drinking-induced malnutrition decreases the synthesis of vitamin K-dependent clotting factors.
• Alcohol prolongs bleeding time when combined with aspirin and NSAIDs.

Renal Disease

• Haemostasis is impaired in patients with chronic renal failure due to impaired platelet production and adhesion.
• A decrease in platelet factor 3 and vasodilation contribute to impaired haemostasis.
• Haemodialysis patients with chronic renal failure who are taking heparin will have impaired haemostasis
• Clinicians should monitor for signs and symptoms of renal failure, especially in patients with poorly controlled hypertension or diabetes.

Disorders of Coagulation

• These can be inherited with Haemophilia A, Haemophilia B (Christmas Disease) and Von Willebrand disease
• These can be acquired with Liver disease and a reduced production of coagulation factors
• Haemotological malignancy results in impaired coagulation
• Anticoagulant drugs also cause coagulation issues

Haemophilia A

• Most common type of Haemophilia, affecting 1 in 5000 males.
• It involves a deficiency of clotting factor VIII and is an X-linked recessive condition.
• Males are affected, while females are carriers and may have reduced factor VIII levels.
• The condition's severity ranges from mild to severe in its effects
• Bleeding that does not stop is the main symptom
• Other symptoms include nosebleeds, bleeding gums, easy bruising, and pain around joints like elbows.

Haemophilia B (Christmas Disease)

• It is less common than Haemophilia A.
• It involves a deficiency in clotting factor IX.
• It also follows an X-linked recessive inheritance pattern.
• Males are affected, and females are carriers.
• It also affects 1 in 5000 males.
• Symptoms are generally the same as in Haemophilia A.

Von Willebrand Disease

• It is the most common hereditary coagulation abnormality, affecting 1% of the population equally in males and females.
• Characterized by a deficiency or dysfunction of von Willebrand factor (vWF).
• vWF acts as a carrier for factor VIII and mediates platelet adhesion and aggregation.
• It has three types with varying severity: mild, moderate, and severe.
• Presentation is similar to platelet dysfunction.
• Treatments include desmopressin, tranexamic acid, and factor VIII replacement.

Antiplatelet Drugs

• Common indications include ischaemic heart disease, previous myocardial infarction, and atrial fibrillation.
• Coronary stent placement, previous stroke, and renal transplant are also indications.
• Examples include Aspirin, Clopidogrel, Dipyridamole, Ticagrelor, and Prasugrel.

Anticoagulant Drugs

• Common indications include stroke, transient ischaemic attack, and deep vein thrombosis.
• Other indications are pulmonary embolism, atrial fibrillation, and heart valve surgery.
• Warfarin and Direct Oral Anticoagulant Drugs (DOACs) are examples
• Rivaroxaban, Apixaban, Edoxaban, and Dabigatran are specific DOACs.
• Injectable Anticoagulants include Dalteparin, Enoxaparin, and Tinzaparin and also Heparin

Warfarin

• Blocks enzymes using vitamin K to produce clotting factors as a vitamin K antagonist.
• Impairs the synthesis of factors II, VII, IX, and X.
• Increases prothrombin time and activated partial thromboplastin time.
• Requires monitoring by measuring International Normalised Ratio (INR).
• Target INR levels range from 2.5-3.5 depending on the indication and are slowly absorbed with a long half-life.
• Begins to take effect only after 8-12 hours and peaks at 36 hours, persisting for 72 hours.
• Interacts with multiple medications.

Direct Oral Anticoagulant Drugs

• Includes Rivaroxaban, Apixaban, and Edoxaban all of which are reversible inhibitors of factor Xa.
• Factor Xa prevents thrombin generation and thrombus development
• Dabitgatran is a reversible competitive thrombin inhibitor.
• It directly inhibits the conversion of fibrinogen to fibrin.
• Action has a rapid onset of action of 1-4 hours, relatively to Warfarin.
• Routine monitoring typically is not required, as they cannot be measured by any INR measurement
• Presents fewer food interactions and is restrictive.
• Only Apixaban, dabigatran, rivaroxaban have reversal factors, edoxaban does not

Heparin

• Presents a short half-life of 1-2 hours and is mainly used intravenously in hospitals for inpatient care.
• It can also be administered subcutaneously
• Minihep reduces the risk of deep vein thrombosis in pregnant women or after surgery and thrombolosis due to myocardial arrest.
• Can be used for IV dialysis to prevent thrombosis in pumps.
• Advice is recommended before invasive dental treatment as there is a bleeding risk.