Bleeding disorders Flashcards
Haemostatic faliure, DIC, Haemophilia, Von Willebrand’s Disease, ITP, TTP, Massive Haemorrhage, Vitamin K deficiency
What is primary haemostatic failure?
Primary haemostatic failure is caused by thrombocytopenia, leading to a lack of platelet adhesion.
What causes primary haemostatic failure?
(1) Marrow failure
(2) Peripheral destruction
both acquired or hereditary conditions
What is secondary haemostatic failure?
Secondary haemostatic failure involves clotting factor deficiencies, which impair fibrin clot formation
What factors contribute to secondary haemostatic failure?
(1) deficiencies in clotting factors, most of which require vitamin K.
(2) Warfarin, as an anticoagulant, causes vitamin K deficiency, affecting factors 10, 7, 9, and 2 (prothrombin
Define Disseminated Intravascular Coagulation (DIC)
Excessive and inappropriate activation of the haemostatic system - Primary, secondary and fibrinolysis (clinical syndrome)
What is the cause of excessive activation of the haemostatic system?
(1) sepsis
(2) obstetric emergencies
(3) malignancy
(4) hypovolaemic shock
(5) ABO incompatibility
What is the pathophysiology of DIC
Microvascular thrombi form, causing end-organ failure, while clotting factor consumption leads to bruising, purpura, and bleeding
What are the clinical features of excessive haemostatic system activation? - DIC
(1) Patients are often acutely ill
(2) with bleeding from various sites and thrombotic events affecting organs like the skin, brain, and kidneys
What is the management for excessive haemostatic system activation? - DIC
(1) The underlying cause should be treated.
(2) Replacement therapy includes platelet transfusions, plasma transfusions, and fibrinogen replacement
What is haemophilia?
An X-linked recessive hereditary disorder characterised by abnormally prolonged bleeding, usually at one or a few sites on each occasion
What are the types of haemophilia and their causes?
Haemophilia A: Factor VIII deficiency (5x more common)
Haemophilia B: Factor IX deficiency
What is the pathophysiology of haemophilia?
(1) No abnormality in primary haemostasis
= Platelet function is normal; the issue is in the coagulation cascade
(2) Bleeding occurs in medium to large blood vessels, often in joints.
(3) Severity depends on the level of factor VIII or IX involved
= Haemophilia is a clotting disorder due to Factor VIII (A) or IX (B) deficiency, impairing the intrinsic pathway. This leads to reduced thrombin, poor fibrin clot formation, and prolonged bleeding, especially in joints and muscles
What are the clinical features of haemophilia?
Mild - Bleeding after injury or surgery
Severe -
(1) Recurrent haemarthroses - bleeding in joint space
(2) Recurrent soft tissue bleeds
(3) Bruising in toddlers
(4) Prolonged bleeding after dental extractions, surgery, and invasive procedures
(5) Joint, muscle bleeding
How is haemophilia diagnosed?
(1) Isolated prolonged APTT
(activated partial thromboplastin time)
(2) coagulation factor assays (VIII for A, IX for B)
(3) genetic testing
How are the affected clotting factors in haemophilia replaced?
Replaced by IV infusions, either prophylactically or in response to bleeding
What is a complication of clotting factor replacement in haemophilia?
Formation of antibodies against the clotting factor, which can make the treatment ineffective
What causes von Willebrand’s disease?
Von Willebrand disease (VWD) is a common inherited bleeding disorder caused by a reduced quantity or function of von Willebrand factor (VWF).
This leads to an increased risk of bleeding, especially among women during their menstrual periods, pregnancy, and childbirth
How do symptoms of von Willebrand disease compare to haemophilia A?
Von Willebrand disease has milder symptoms compared to haemophilia A, with ;
(1) no haemarthrosis (Bleeding into a joint space)
(2) more common occurrences of epistaxis (nose bleeds)
(3) and menorrhagia (Excessively heavy menstrual bleeding)
(4) Haemophilia is more common in men than von villebrand sydrome is
What is the cause of Immune Thrombocytopenic Purpura (ITP)?
Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterised by a reduction in circulating platelets.
In children, it usually follows a viral infection and is self-limiting
Autoimmune body produces antibodies agaisnt its thrombocytes or platelets
What is the difference between primary and secondary ITP?
(1) Primary ITP occurs in isolation
(2) while secondary ITP is associated with other conditions such as autoimmune disorders, viral infections, or lymphoproliferative disorders
What is the pathophysiology of ITP?
ITP is caused by a type II hypersensitivity reaction, where antibodies target and destroy platelets, often triggered by viral infections or other factors
What are the common clinical features of ITP?
(1) Easy or excessive bruising (purpura)
(2) Superficial bleeding into the skin that appears as a rash of pinpoint-sized reddish-purple spots (petechiae), usually on the lower legs
(3) Prolonged bleeding from cuts
(4) Spontaneous bleeding from the gums or nose - ITP presents with mucocutaneous bleeding
(5) Blood in urine or stools
(6) Unusually heavy menstrual flow in females
(7) It is most common in children under 10
How is ITP diagnosed?
(1) Full Blood Count (FBC) - isolated thrombocytopenia
(2) blood film and exclusion of differential diagnoses.
(3) Management generally involves a ‘watch and wait’ approach due to the high rate of spontaneous remission
What causes Thrombotic Thrombocytopenic Purpura (TTP)?
By a deficiency of the metalloproteinase ADAMTS13, which is associated with triggers such as medication, AIDS, and malignancy
What is the classic pentad of symptoms in TTP?
The classic pentad includes
(1) fever
(2) hemolytic anaemia
(3) thrombocytopenia
(4) acute renal failure
(5) neurological symptoms
What is the mainstay of treatment for TTP?
IV plasma exchange
= If unresponsive, splenectomy may be considered for chronic relapses
A 5-year-old male patient presents to the emergency department with fever, headache, and vomiting.
On physical examination, he is pyrexial, with neck stiffness and a petechial skin rash. He is admitted to the intensive care unit but deteriorates, with evidence of blood oozing from the cannula sites, gingival bleeding, and hypotension
What is the correct coagulation profile consistent with the most likely diagnosis?
Decreased fibrinogen, decreased platelets, elevated D-dimer
= is DIC
DIC because the patient has sepsis, petechial rash and bleeding signs
What is a characteristic finding in DIC?
schistocytes on blood film
Patients with DIC commonly present with what?
(1) Excessive bleeding
(2) Fever
(3) Confusion
(4) Potential coma
Physical signs of DIC include what?
(1) Petechiae
(2) Bruising
(3) Confusion
(4) Hypotension
What would DIC clotting profile show in tests?
(1) Increased prothrombin time
(2) increased APTT
(3) decreased fibrinogen
(4) Increased D Dimer
Prolonged PT and APTT with low platelets point to what disease?
Disseminated intravascular coagulation
A 43-year-old patient presents to the hospital feeling generally unwell. For the last 3 months, he has noticed weight loss and a reduced appetite.
More recently, he has had blood in his urine, easy bruising, and oozing from his gums whenever he brushes his teeth. In the past few days, he has noticed a few digits on his lower limbs go cold and turn dusky.
His blood tests are shown below:
Haemoglobin: 72g/L (110-180) Platelets: 36 x 10^9/L (150-400) Blood film: schistocytes present INR: 4.5 (<1.1) APTT: 100 seconds (27-41)
What is the most likely diagnosis?
Disseminated intravascular coagulation (DIC)
A concerned mother brings her 6-year-old daughter to paediatric A&E because she has noticed a new non-blanching rash and is worried her daughter has meningitis. The mother reports that her daughter has complained of a sore throat and cough over the past week, which has improved. On examination, the girl’s legs are covered with a petechial rash. Blood tests show low platelets but no other abnormalities. The urine dipstick is normal.
What is the most likely diagnosis?
Immune thrombocytopenic purpura
A concerned mother brings her 5-year-old son to paediatric A&E because she has noticed a new non-blanching rash and is worried her son has meningitis. The mother reports that her son has complained of a sore throat and cough over the past few days, which has improved. On examination, the boy’s legs are covered with a petechial rash. Blood tests show low platelets but no other abnormalities.
Given the most likely diagnosis of immune thrombocytopenic purpura, what is the best next step in managing this patient?
Reassure the mother this is a self-limiting illness
Isolated low platelet count of unknown cause indicates what condition?
Immune thrombocytopenia
What drug should be avoided in children with ITP?
Ibuprofen
What blood results on the clotting screen would you expect to see in Von Willebrand’s disease?
PT time is normal but APTT is prolonged. Bleeding time is prolonged
What is the mode of inheritance of Von Willebrand disease?
Autosomal dominant
What are the main ways to treat a patient with Von Willebrand disease who is bleeding?
(1) Desmopressin
(2) Tranexamic acid
(3) Factor VIII concentrate (severe bleeding)
A 19-year-old woman presents to the emergency department after a tooth extraction earlier in the day. She has a history of heavy periods since menarche but is otherwise fit and well. She has a family history of a bleeding disorder. On examination, there is still bleeding from the tooth extraction site, but no other abnormalities are noted.
What is the best next step in the management of this patient?
Desmopressin
Define von Willebrand disease
von Willebrand disease (vWD) is an autosomal dominant bleeding disorder characterised by episodes of prolonged mucosal bleeding (eg. epistaxis, gum bleeding) and menorrhagia
It is caused by a deficiency/loss of function of von Willebrand factor (VWF), which usually mediates platelet aggregation and factor VIII activation
First-line treatment in most subtypes of vWD is what?
Desmopressin
A 17-year-old boy is referred for blood tests due to recurrent epistaxis and bruising that appears to spontaneously develop on his shins. His father suffers similar symptoms.
Blood tests are as follows:
(1) Prothrombin time (PT): 12 seconds (10-14 seconds)
(2) Activated partial thromboplastin time (APTT): 37 seconds (25-35 seconds)
(3) Bleeding time: prolonged
What is the most likely diagnosis?
Von Willebrand disease
A 16-year-old girl with known iron deficiency anaemia attends her GP complaining of continuing fatigue and exercise intolerance, despite treatment with iron tablets.
On further questioning, you learn that her period is every 28 days with heavy bleeding for seven days. She also explains how she bruises easily, and her gums often bleed when she brushes her teeth. She has no other medical history. Further investigations reveal that she has normal platelet levels, but they do not agglutinate properly
Which investigation findings are also likely?
Normal prothrombin time
A 19-year-old woman is referred to haematology outpatients with recurrent and persistent nosebleeds and severe bruising. There is a dominant family history of Von Willebrand disease.
What is the expected pattern on routine clotting tests?
Normal platelets
Prolonged bleeding time
Prolonged APTT
Normal PT and TT
A 17-year-old female has prolonged bleeding after a tooth extraction. She tells her dentist that her gums often bleed when she brushes her teeth and she gets frequent nosebleeds. Her mother also has similar problems and she thinks there may be a bleeding disorder that runs in her family.
Which clotting factor is most likely to be affected in this patient?
Factor 8
Key signs and symptoms of Von Willebrand disease include what?
(1) prolonged bleeding from minor wounds
(2) easy bruising
(3) menorrhagia
(4) epistaxis
(5) GI bleeding
(6) menstrual bleeding
How does Haemophilia often present in toddlers?
Presents as failure to walk or walking late due to bleeding into joints
At what age do patients tend to present with Hereditary Hemochromatosis?
(1) Women can present later than men due to regular iron loss every month (menstruation)
(2) Men tend to present in their forties or fifties
What are the two types of Haemophilia?
The two types of Haemophilia are
Type A (deficiency in Factor 8)
Type B (deficiency in Factor 9)
A mother attends the genetics clinic. She is concerned as she has become pregnant and is having a boy. Her father died at age 25 from internal bleeding. She suffers from mild symptoms of occasional nosebleeds and prolonged bleeding times.
Her investigation results are shown below:
(1) Activated partial thromboplastin time (APTT): 50 seconds (24-37 seconds)
(2) Factor VIII: 90IU/dL (50-150IU/dL)
(3) Factor IX: 40IU/dL (65-150IU/dL)
She is worried about the chance that her son will inherit the disease.
What is the chance her son will inherit her underlying genetic disease? and why?
50%
= This patient is a carrier of haemophilia B. This is evidenced by the fact that her father was affected, and she has reduced Factor IX activity. Haemophilia B is an X-linked condition. Therefore, males with the condition will always pass the affected X chromosome to daughters but never to sons. Mothers who are carriers of haemophilia B have a 50% chance of a male child being affected by haemophilia B
What do blood tests show in haemophilia?
(1) Clotting profile - APTT is elevated
(2) vWF antigen is normal in haemophilia A
(3) Defective platelet function
Management for minor, major and severe bleeds
Minor
= Minor bleeds in patients with Haemophilia A can be managed with desmopressin
Major
= recombinant factor VIII or IX
severe
= use of regular prophylactic recombinant clotting factor treatment, physiotherapy and education
A 24-year-old presents to the emergency department with severe haemarthrosis. He has a background of haemophilia A, diagnosed shortly after birth. On examination, his chest is clear, and his observations are as follows:
(1) Heart rate: 110 beats per minute
(2) Blood pressure: 105/87 mmHg
(3) Respiratory rate: 12 breaths per minute
(4) SpO2: 100% on room air
What is the most appropriate treatment?
Recombinant factor VIII
A 3-year-old boy presents to the GP with his mother following the development of severe bruising after minor trauma. On examination, there is a large, deep ecchymosis along the patient’s right thigh (there is nil else of note).
Blood tests reveal a normal blood count, urea & electrolytes and liver function. A coagulopathy screen reveals a normal bleeding time, normal PT (INR) and normal fibrinogen; but the APTT is prolonged.
What is the single most likely diagnosis? and explain why your answer
Haemophilia A
= Haemophilia A is an inherited bleeding disorder, which presents in early life with deep bleeding (haemarthrosis, muscular haematomas) associated with deranged coagulation tests (prolonged APTT) and a normal platelet count.
What will the confirm the diagnosis of haemophilia A?
Factor VIII assay
When is factor VIII normal?
Haemophilia B
An 11-year-old boy presents to the GP with his mother with several nosebleeds and excessive bleeding from his gums after visiting the dentist. He says his 8-year-old sister does not have any of these symptoms, but his maternal grandfather used to have regular hospital appointments for an injection. His blood tests show a prolonged APTT.
Given the most likely diagnosis, which of the following is the most likely pattern of inheritance?
X Linked Recessive
A 2-year-old boy with a diagnosis of haemophilia B attends the haematology clinic. He has recently had an admission to the hospital with a right knee joint hemarthrosis. He is currently well, with no symptoms and no clinical evidence of joint deformity.
What treatments are most appropriate to minimise the risk of complications in this patient?
Factor IX replacement
A 35-year-old man presents with a history of recurrent joint bleeds and easy bruising. His blood test results reveal a prolonged activated partial thromboplastin time (aPTT) with a normal prothrombin time (PT) and thrombin time (TT)
What bleeding disorder is this?
Haemophilia A
A patient who is 36 weeks pregnant is seen during the obstetrics ward round. She has heard some of the staff on the ward talking about vitamin K and asks whether this is something her baby will need. The doctor explains that babies are born deficient in vitamin K so all newborns are offered vitamin K to reduce their risk of bleeding and a condition called haemorrhagic disease of the newborn.
What is the correct way to give vitamin K to newborns?
Intramuscular vitamin K on the first day of life
A 6-month-old exclusively breastfed infant presents with bruising, bleeding from gums and nose, and blood in the diaper.
What is the most likely cause of his symptoms? and why is this the answer?
Vitamin K deficiency
= Breast milk has low levels of vitamin K, which is essential for the production of coagulation factors. Infants who are exclusively breastfed may have a deficiency of vitamin K, which can lead to bleeding tendencies
An 8-year-old boy presents to the GP with his mother following the development of several blood blisters in his mouth.
Blood tests reveal an isolated thrombocytopenia (30) and a prolonged bleeding time, but are otherwise normal.
What is the single most likely diagnosis? and why is that your answer?
Immune thrombocytopenic purpura
Given the presence of oral blood blisters, associated isolated thrombocytopenia (30) and prolonged bleeding time
When would Observation be the best course of action for the management of a patient with Immune thrombocytopenic purpura (ITP)?
Platelet count of >30 × 109/L with no symptoms or additional risk factors
When would corticosteroids (eg, oral prednisolone) be the correct management for a patient with Immune thrombocytopenic purpura (ITP)?
Patients with a platelet count of
(1) <30 × 109/L or a platelet count >30 × 109/L + features of minor bleeding/high risk
(e.g. the high-risk profession or upcoming surgery)
Treatment for patients diagnosed with ITP
Treatmentmay be required if the patient is actively bleeding or severe thrombocytopenia (platelets ≤10):
- Prednisolone - IV immunoglobulins - Blood transfusionsif required - Platelet transfusionsonly work temporarily
“Bleeding when they brush their teeth” suggests what?
ITP
Immune vs thrombotic thrombocytopaenia. Who is more healthier?
Thrombotic patients are more unwell
What are the differences between haemophilia A and haemophilia B?
Haemophilia A and B have no significant difference in symptoms. Both cause:
(1) Spontaneous bleeding (joints, muscles)
(2) Prolonged bleeding after injury/surgery
(3) Haemarthrosis (joint swelling, pain, stiffness)
(4) Easy bruising
The only difference is cause:
Haemophilia A → Factor VIII deficiency
Haemophilia B → Factor IX deficiency
Diagnosis is confirmed by factor level testing
Which bleeding symptoms are more common in Von Willebrand disease (VWD) compared to Haemophilia?
Von Willebrand disease is more likely to cause nosebleeds (epistaxis) and heavy menstrual bleeding (menorrhagia)
= affecting primary haemostasis (platelet adhesion).
Haemophilia primarily causes deep tissue bleeding (joints, muscles) due to a deficiency in clotting factors (Factor VIII or IX)
= affecting secondary haemostasis
What are the typical blood results for Haemophilia
Platelet count: Normal
Bleeding time: Normal
Prothrombin time (PT): Normal
APTT: Prolonged
What are the typical blood results for DIC?
Platelet count: Low
Bleeding time: Prolonged
Prothrombin time (PT): Prolonged
APTT: Prolonged
Fibrinogen: Low
INR: Prolonged
D-dimer: Elevated
What are the typical blood results for TTP?
Platelet count: Low
Bleeding time: Prolonged
Prothrombin time (PT): Normal
APTT: Normal
LDH: Elevated
Schistocytes: Present on peripheral blood smear
What are the typical blood results for ITP?
Platelet count: Low
Bleeding time: Prolonged
Prothrombin time (PT): Normal
APTT: Normal
What are the typical blood results for Vitamin K deficiency or Warfarin overdose?
Platelet count: Normal
Bleeding time: Normal
Prothrombin time (PT): Prolonged
APTT: Prolonged
INR: Prolonged
A 25-year-old woman presented with bleeding from her nose. She had not had similar problems before and was usually well. Her observations are normal.
Test Result Normal range
(1) Haemoglobin 130 g/L
(M) 130 - 170, (F) 115 - 155
(2) Platelet count 20 × 109/L
150 - 450 × 109/L
What is the most appropriate first-line treatment for this condition?
Oral corticosteroids
= First line for ITP
What are the differences between Haemophilia, ITP, TTP, Von Willebrand disease and DIC?
Haemophilia
= (1) Deep tissue bleeding, joint and muscle bleeds
(2) Normal platelets, prolonged APTT
ITP
= (1) Mucosal bleeding (nosebleeds, gum bleeding), Petechiae, purpura brusing
(2) Low platelets, normal PT/APTT
TTP
= (1) Neurological symptoms (headache, confusion, seizures), hemolysis
(2) Low platelets, Schistocytes, normal PT/APTT
Von Willebrand Disease
= (1) Mucosal bleeding (nosebleeds, heavy periods)
(2) Normal platelets, prolonged bleeding time, normal PT, prolonged APTT
DIC
= (1) Widespread bleeding (from multiple sites), organ failure
(2) Low platelets, prolonged PT/APTT, elevated D-dimer, reduced fibrinogen
fever, headache, vomiting, petechial rash, shock
Suggests meningococcal infection
=classic cause of DIC
What bleeding disorders respond well to Desmopressin (DDAVP)?
Von Willebrand Disease
Mild Haemophilia A
What bleeding disorders respond well to steroids?
ITP
Acquired Haemophilia
Atypical HUS
A 25-year-old woman comes to the clinic due to easy bruising and heavy menstrual bleeding. Laboratory studies show decreased factor VIII and ristocetin cofactor activity and decreased VWF antigen.
What disease is this describing?
Von Willebrand disease
Factor V Leiden is associated with what?
Haemophilia B
Why do von Willebrand disease patients often have a history of bleeding?
It’s inherited, so family history is common. Symptoms like excessive bleeding usually start early in life and has been seen before.
A 12-year-old boy with a past medical history of Haemophilia A is about to undergo dental extraction. To prevent excessive bleeding, a subcutaneous injection of desmopressin was given immediately before the procedure.
What is the mechanism of action of desmopressin when used to prevent bleeding in Haemophilia A?
Releases von Willebrand factor from its storage sites in endothelial cells
A 72-year-old man has just undergone an emergency repair for a ruptured abdominal aortic aneurysm. Preoperatively he was taking aspirin, clopidogrel and warfarin. Intraoperatively he received 5000 units of unfractionated heparin before application of the aortic cross clamp. His blood results on admission to the critical care unit are as follows:
Full blood count
Hb 8 g/dl
Platelets 40 * 109/l
WBC 7.1 * 109/l
His fibrin degradation products are measured and found to be markedly elevated. What accounts for these results?
DIC
A 34-year-old man presents to his GP with a 6-month history of foul-smelling, fatty stools and weight loss. On examination of the patient’s abdomen, no masses or organomegaly are felt. The GP does notice several bruises on the patient’s abdomen, yet the patient denies any trauma. The patient’s sister has coeliac disease. He reports playing rugby as a child and did not notice unusual bruising. The GP orders several blood tests, shown below:
Hb 138 g/L Male: (135-180)
Female: (115 - 160)
Platelets 260 * 109/L (150 - 400)
WBC 6.0 * 109/L (4.0 - 11.0)
Prothrombin time (PT) 19 secs (10-14 secs)
Activated partial thromboplastin time (APTT) 36 secs (25-35 secs)
What is the most likely cause of the patient’s bruising?
Vitamin K deficiency
A 48-year-old man presents to the hospital complaining of easy bruising. He was recently discharged from the hospital after recovering from community-acquired pneumonia requiring prolonged intravenous and later oral broad-spectrum antibiotics. His vital signs are normal. Laboratory tests are significant for a prolonged prothrombin time, a prolonged partial thromboplastin time, and a normal platelet count.
Which is the most likely underlying cause of his condition?
Vitamin k Deficiency
prolonged prothrombin and prolonged partial thromboplastin + normal platelet = what disease
Vitamin K deficiency
A 40-year-old female is referred to medical assessment unit by her physician for querying thrombotic thrombocytopenic purpura (TTP) after she presented with a temperature of 38.9ºC. Her subsequent urea and electrolytes showed deteriorating renal function with a creatinine 3 times greater than her baseline.
What is the underlying pathophysiology of TTP?
TTP is caused by the failure to cleave vWF normally
Idiopathic thrombocytopenic purpura (ITP) is a condition characterised by autoimmune destruction of platelets.
What type of hypersensitivity is this defined as?
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