Haematology Flashcards
What is the definition of anaemia?
Anaemia is defined as a low concentration of haemoglobin in the blood. It is a consequence of an underlying disease, not a disease itself. The prefix “an-“ means without, and “-aemia” refers to blood.
What does mean cell volume (MCV) indicate, and what are the normal ranges for men and women?
Mean cell volume (MCV) refers to the size of red blood cells and is highly relevant in anaemic patients. The normal ranges are:
Women: 120 – 165 grams/litre for haemoglobin; 80-100 femtolitres for MCV.
Men: 130 -180 grams/litre for haemoglobin; 80-100 femtolitres for MCV.
How is anaemia classified based on mean cell volume (MCV)?
Anaemia is divided into three categories based on MCV:
Microcytic anaemia (low MCV)
Normocytic anaemia (normal MCV)
Macrocytic anaemia (large MCV)
What are the causes of microcytic anaemia?
The mnemonic “TAILS” helps remember the causes of microcytic anaemia:
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
What is a common cause of anaemia of chronic disease, and how is it treated?
Anaemia of chronic disease often occurs with chronic kidney disease due to reduced production of erythropoietin by the kidneys, which stimulates red blood cell production. Treatment involves administering erythropoietin.
What are the causes of normocytic anaemia?
The causes of normocytic anaemia are:
A – Acute blood loss
A – Anaemia of chronic disease
A – Aplastic anaemia
H – Haemolytic anaemia
H – Hypothyroidism
What differentiates megaloblastic anaemia from normoblastic macrocytic anaemia?
Megaloblastic anaemia results from impaired DNA synthesis, preventing normal cell division, leading to large, abnormal cells. It is caused by:
B12 deficiency
Folate deficiency
Normoblastic macrocytic anaemia is caused by:
Alcohol
Reticulocytosis (from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs, such as azathioprine
What are the symptoms of anaemia?
There are many generic symptoms of anaemia:
Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of other conditions, such as angina, heart failure or peripheral arterial disease
Symptoms specific to iron deficiency anaemia include:
Pica (dietary cravings for abnormal things, such as dirt or soil)
Hair loss
What are the signs of anaemia?
Generic signs of anaemia include:
Pale skin
Conjunctival pallor
Tachycardia
Raised respiratory rate
Signs of specific causes of anaemia include:
–> Koilonychia refers to spoon-shaped nails and can indicate iron deficiency anaemia
–> Angular cheilitis can indicate iron deficiency anaemia
–> Atrophic glossitis is a smooth tongue due to atrophy of the papillae and can indicate iron deficiency anaemia
–> Brittle hair and nails can indicate iron deficiency anaemia
–> Jaundice can indicate haemolytic anaemia
–> Bone deformities can indicate thalassaemia
–> Oedema, hypertension and excoriations on the skin can indicate chronic kidney disease
What are the investigations for anaemia?
Blood tests depend on the suspected cause. Possible blood tests include:
–> Full blood count for haemoglobin and mean cell volume
–> Reticulocyte count (indicates red blood cell production)
–> Blood film for abnormal cells and inclusions
–> Renal profile for chronic kidney disease
–> Liver function tests for liver disease and bilirubin (raised in haemolysis)
–> Ferritin (iron)
–> B12 and folate
–> Intrinsic factor antibodies for pernicious anaemia
–> Thyroid function tests for hypothyroidism
–> Coeliac disease serology (e.g., anti-tissue transglutaminase antibodies)
–> Myeloma screening (e.g., serum protein electrophoresis)
–> Haemoglobin electrophoresis for thalassaemia and sickle cell disease
–> Direct Coombs test for autoimmune haemolytic anaemia
A colonoscopy and oesophagogastroduodenoscopy (OGD) are indicated for unexplained iron deficiency anaemia to exclude gastrointestinal cancer as a source of bleeding.
A bone marrow biopsy is indicated for unexplained anaemia or possible malignancy (e.g., leukaemia or myeloma).
FIT test - GI bleed - cancer
What is the pathophysiology of thalassemia?
Thalassaemia is related to a genetic defect in the protein chains that make up haemoglobin. Normal haemoglobin consists of 2 alpha and 2 beta globin chains. Defects in the alpha globin chains lead to alpha thalassaemia. Defects in the beta-globin chains lead to beta thalassaemia. Both conditions are autosomal recessive. The overall effect is varying degrees of anaemia, depending on the type and mutation
In patients with thalassaemia the red blood cells are more fragile and break down more easily. The spleen acts as a sieve to filter the blood and remove older blood cells. In patients with thalassaemia, the spleen collects all the destroyed red blood cells, resulting in splenomegaly.
The bone marrow expands to produce extra red blood cells to compensate for chronic anaemia. This causes susceptibility to fractures and prominent features, such as a pronounced forehead and malar eminences (cheekbones).
What are the potential signs and symptoms of thalassemia?
Microcytic anemia (low mean corpuscular volume)
Fatigue
Pallor
Jaundice
Gallstones
Splenomegaly
Poor growth and development
Pronounced forehead and malar eminences
What are the investigations for thalassemia?
–> Full blood count shows microcytic anaemia.
–> Haemoglobin electrophoresis is used to diagnose globin abnormalities.
–> DNA testing can be used to look for the genetic abnormality
–> Pregnant women are offered a screening test for thalassemia at booking
Why can iron overload occur in thalassemia?
–> from the faulty creation of red blood cells
–> recurrent transfusions
–> Increased absorption of iron in the gut in response to anemia
Patients with thalassaemia have serum ferritin levels monitored to check for iron overload
What are the signs and symptoms of iron overload with thalassemia?
Iron overload in thalassemia causes effects similar to hemochromatosis:
Fatigue
Liver cirrhosis
Infertility
Impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
What is the management of iron overload in thalassemia patients?
limiting transfusions and performing iron chelation (Desferoxamine)
What is alpha thalassemia?
Alpha-thalassaemia is caused by defects in alpha globin chains. The gene coding for this protein is on chromosome 16.
What is the management of alpha thalassemia?
–> Monitoring the full blood count
–> Monitoring for complications
–> Blood transfusions
–> Splenectomy may be performed
–> Bone marrow transplant can be curative
What is beta thalassemia?
Beta-thalassaemia is caused by defects in beta globin chains. The gene coding for this protein is on chromosome 11.
The gene defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in the beta-globin protein at all. Based on the type of defect, beta-thalassemia can be split into three types:
Thalassemia minor
Thalassaemia intermedia
Thalassemia major
What is the patho of beta thalassaemia minor
Patients with beta thalassaemia minor are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal gene
What does thalassemia minor cause?
mild microcytic anaemia
What is the management of beta-thalassemia minor?
only require monitoring and no active treatment.
What is the patho of beta thalassemia intermedia
Patients with beta thalassaemia intermedia have two abnormal copies of the beta globin gene. This can be either two defective genes or one defective gene and one deletion gene.
What does thalassemia intermedia cause?
more significant microcytic anaemia
What is the management of beta-thalassemia intermedia?
monitoring and occasional blood transfusions. When they require more transfusions, they may require iron chelation to prevent iron overload.
What is the patho of thalassemia major?
Patients with beta thalassaemia major are homozygous for the deletion genes. They have no functioning beta globin genes at all. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.
What does beta thalassemia major cause?
–> Severe microcytic anaemia
–> Splenomegaly
–> Bone deformities
What is the management of thalassemia major?
Management involves regular transfusions, iron chelation, and splenectomy. Bone marrow transplants can potentially be curative.
What is the most common cause of anaemia worldwide?
Iron deficiency is the most common cause of anaemia globally.
Why does iron deficiency cause anaemia?
Iron is needed to make haemoglobin in red blood cells. A deficiency in iron leads to a reduction in red blood cells/haemoglobin, resulting in anaemia.
What are the main causes of iron deficiency anaemia?
–> Excessive blood loss:
Chronic gastrointestinal bleeding (e.g., peptic ulcers, colorectal cancer, inflammatory bowel disease)
Heavy menstrual bleeding (menorrhagia)
Post-surgical blood loss
Trauma
–> Inadequate dietary intake:
Insufficient iron-rich foods (e.g., red meat, leafy greens)
Vegetarian or vegan diets without proper iron supplementation
–> Poor intestinal absorption:
Conditions affecting absorption (e.g., coeliac disease, Crohn’s disease)
Post-gastrectomy or bariatric surgery
Chronic use of medications that reduce stomach acid (e.g., proton pump inhibitors)
–> Increased iron requirements:
Pregnancy and breastfeeding
Rapid growth during infancy, childhood, and adolescence
What are the features of iron deficiency anaemia?
Fatigue
Shortness of breath on exertion
Palpitations
Pallor
Nail changes: this includes koilonychia (spoon-shaped nails)
Hair loss
Atrophic glossitis
Post-cricoid webs
Angular stomatitis
What are the key elements to inquire about when taking a history for iron deficiency anaemia?
Key history points for investigating iron deficiency anaemia include:
Dietary changes (e.g., vegetarian or vegan diet)
Medication history (e.g., proton pump inhibitors)
Menstrual history (e.g., heavy periods/menorrhagia)
Weight loss (unexplained weight loss may suggest malignancy)
Changes in bowel habit (e.g., diarrhoea, constipation, blood in stool, which could suggest GI issues)
What does a full blood count (FBC) typically show in iron deficiency anaemia?
Hypochromic microcytic anaemia: Red blood cells are smaller than normal and have reduced haemoglobin concentration.
What is the significance of serum ferritin in diagnosing iron deficiency anaemia?
–> Low serum ferritin indicates low iron stores and suggests iron deficiency anaemia.
Note: Ferritin is an acute phase reactant, meaning it can be falsely elevated in states of inflammation. A raised ferritin does not rule out iron deficiency if there is concurrent inflammation. Other iron studies may be needed in these cases.
What is the role of total iron-binding capacity (TIBC) and transferrin in iron deficiency anaemia?
TIBC/transferrin is usually high in iron deficiency anaemia, reflecting low iron stores.
Transferrin saturation is low because there is less iron available to bind to transferrin.
What are the key findings on a blood film in iron deficiency anaemia?
Anisopoikilocytosis: Red blood cells of varying sizes and shapes
Target cells
‘Pencil’ poikilocytes
When should endoscopy be considered in patients with iron deficiency anaemia?
Endoscopy should be considered to rule out malignancy in:
Males and post-menopausal females with unexplained iron-deficiency anaemia.
Patients with haemoglobin ≤10 in post-menopausal women and ≤11 in men should be referred to a gastroenterologist within 2 weeks.
What are the investigations for iron deficiency anaemia?
–> History Taking
Dietary changes (e.g., vegetarian or vegan diet)
Medication history (e.g., proton pump inhibitors)
Menstrual history (e.g., heavy periods/menorrhagia)
Weight loss (unexplained weight loss, which may suggest malignancy)
Changes in bowel habit (e.g., diarrhoea, constipation, or blood in stool, suggesting gastrointestinal issues)
–> Full Blood Count (FBC)
Hypochromic microcytic anaemia (small, pale red blood cells due to reduced haemoglobin concentration)
–> Serum Ferritin
Low ferritin: Indicates low iron stores.
Caution: Ferritin may be falsely elevated during inflammation, which could obscure iron deficiency.
–> Total Iron-Binding Capacity (TIBC) / Transferrin
High TIBC/transferrin: Reflects low iron stores.
Low transferrin saturation: Indicates less iron available to bind to transferrin.
–> Blood Film
Anisopoikilocytosis: Red blood cells of varying sizes and shapes.
Target cells
Pencil poikilocytes
–> Endoscopy
Indication: To rule out malignancy, especially in males and post-menopausal females with unexplained iron deficiency anaemia.
Referral criteria: Post-menopausal women with haemoglobin ≤10 and men with haemoglobin ≤11 should be referred to a gastroenterologist within 2 weeks.
What are the management options for iron deficiency anaemia in adults without a clear underlying cause?
–> Investigate Further
Colonoscopy and OGD to rule out malignancy in adults with new iron deficiency anaemia, unless there is an obvious cause (e.g., heavy menstruation, pregnancy).
–> Treatment Options
- Oral Iron (e.g., ferrous sulphate, ferrous fumarate):
Expected haemoglobin rise of 20 g/L in the first month.
Common side effects: constipation, black stools.
Prophylactic supplementation for recurrent cases.
–> Iron Infusion (e.g., IV CosmoFer):
Rapid iron boost, but small risk of allergic reactions and anaphylaxis.
Avoid during infections due to risk of bacterial growth.
–> Blood Transfusion:
For severe anaemia.
What are the key causes of vitamin B12 deficiency?
Answer:
Pernicious anaemia (autoimmune condition affecting intrinsic factor production)
Insufficient dietary B12 (especially in a vegan diet, as B12 is mostly found in animal products)
Medications that reduce B12 absorption (e.g., proton pump inhibitors and metformin)
What is pernicious anaemia?
–> Autoimmune condition invovling antibodies against the parietal cells or intrinsic factor
What is the pathophysiology of pernicious anaemia,and what autoantibodies are used for diagnosis?
–> Pathophysiology:
The parietal cells in the stomach produce intrinsic factor, which is essential for vitamin B12 absorption in the distal ileum.
In pernicious anaemia, autoantibodies target the parietal cells or intrinsic factor, leading to a lack of intrinsic factor and impaired absorption of vitamin B12.
Autoantibodies for Diagnosis:
Intrinsic factor antibodies (first-line investigation)
Gastric parietal cell antibodies (less helpful)
What are the neurological symptoms of pernicious anaemia?
–> Neurological Symptoms of B12 Deficiency:
Peripheral neuropathy (numbness or paraesthesia)
Loss of vibration sense
Loss of proprioception
Visual changes
Mood and cognitive changes
How is Vitamin B12 deficiency managed, and what are the specific recommendations for pernicious anaemia?
–> Initial Treatment with Intramuscular Hydroxocobalamin:
- No neurological symptoms: 3 times weekly for 2 weeks.
- Neurological symptoms: Alternate days until there is no further improvement.
–> Maintenance Treatment:
- Pernicious anaemia: Injections every 2-3 months for life.
- Diet-related deficiency: Oral cyanocobalamin or injections twice yearly.
–> Important Consideration:
If both B12 and folate deficiency are present, treat the B12 deficiency first. Treating folate deficiency before correcting B12 can lead to subacute combined degeneration of the spinal cord.
What are the inherited and acquired causes of haemolytic anaemia?
Inherited Causes:
Hereditary spherocytosis
Hereditary elliptocytosis
Thalassaemia
Sickle cell anaemia
G6PD deficiency
Acquired Causes:
Autoimmune haemolytic anaemia
Alloimmune haemolytic anaemia (e.g., transfusion reactions, haemolytic disease of the newborn)
Paroxysmal nocturnal haemoglobinuria
Microangiopathic haemolytic anaemia
Prosthetic valve-related haemolysis
What are the triad of features in haemolytic anaemia?
–> Anaemia
–> splenomegaly
–> jaundice
What are the investigations for haemolytic anaemia?
–> Full blood count shows a normocytic anaemia
–> Blood film shows schistocytes (fragments of red blood cells)
–> Direct Coombs test is positive in autoimmune haemolytic anaemia (not in other types)
What is hereditary spherocytosis, and how is it inherited?
Hereditary spherocytosis is the most common inherited haemolytic anaemia in northern Europeans. It is an autosomal dominant condition that causes fragile, sphere-shaped red blood cells, which break down easily.
What are the clinical features of hereditary spherocytosis?
Clinical features include:
Anaemia
Jaundice
Gallstones
Splenomegaly
Aplastic crisis (especially after parvovirus infection)
Positive family history is often noted.
What are the key diagnostic findings in hereditary spherocytosis?
Diagnostic findings include:
Raised mean corpuscular haemoglobin concentration (MCHC) on a full blood count.
Raised reticulocyte count due to rapid turnover of red blood cells.
Spherocytes visible on a blood film.
How is hereditary spherocytosis managed?
Management includes:
Folate supplementation to support red blood cell production.
Blood transfusions as needed.
Splenectomy for long-term control.
Cholecystectomy if gallstones become problematic
What is hereditary elliptocytosis, and how is it inherited?
Hereditary elliptocytosis is an autosomal dominant condition where the red blood cells are ellipse-shaped instead of the typical round shape. It is similar to hereditary spherocytosis.
What causes G6PD deficiency and how is it inherited?
G6PD deficiency is caused by a defect in the gene coding for glucose-6-phosphate dehydrogenase (G6PD), an enzyme that protects cells from oxidative damage. It is an X-linked recessive genetic condition, meaning males are more often affected, and females are typically carriers.
What triggers acute episodes of haemolytic anaemia in G6PD deficiency?
Acute episodes of haemolytic anaemia in G6PD deficiency are triggered by:
Infections
Certain drugs, such as ciprofloxacin, sulfonylureas (e.g., gliclazide), and sulfasalazine
Fava beans (broad beans)
What are the key clinical features of G6PD deficiency?
Key features of G6PD deficiency include:
Jaundice (often in the neonatal period)
Gallstones
Anaemia
Splenomegaly
Heinz bodies on a blood film
How is G6PD deficiency diagnosed?
G6PD deficiency is diagnosed by performing a G6PD enzyme assay to assess the activity of the enzyme.
What is a key exam tip to remember regarding G6PD deficiency?
Look out for a male patient who becomes jaundiced and anaemic after:
Eating fava beans
Developing an infection
Taking antimalarials These are common triggers of G6PD deficiency.
What is autoimmune haemolytic anaemia (AIHA)?
AIHA occurs when antibodies are created against the patient’s red blood cells, leading to their destruction (haemolysis).
How are the two types of autoimmune haemolytic anaemia classified?
AIHA is classified into two types: warm and cold, based on the temperature at which the auto-antibodies destroy red blood cells.
What characterises warm autoimmune haemolytic anaemia?
Warm AIHA is the more common type, where haemolysis occurs at normal or above-normal temperatures and is usually idiopathic.
What is cold-reactive autoimmune haemolytic anaemia also known as?
Cold-reactive AIHA is also called cold agglutinin disease.
At what temperature do antibodies cause agglutination in cold autoimmune haemolytic anaemia?
Agglutination occurs at lower temperatures, typically below 10ºC.
What are some potential secondary causes of cold autoimmune haemolytic anaemia?
Cold AIHA can be secondary to conditions like lymphoma, leukaemia, systemic lupus erythematosus, and infections such as mycoplasma, EBV, CMV, and HIV.
What are the main management options for autoimmune haemolytic anaemia?
Management includes blood transfusions, prednisolone, rituximab (a monoclonal antibody against B cells), and splenectomy.
What is alloimmune haemolytic anaemia?
Alloimmune haemolytic anaemia occurs due to foreign red blood cells or foreign antibodies, typically in transfusion reactions or haemolytic disease of the newborn.
What happens during haemolytic transfusion reactions?
In haemolytic transfusion reactions, the immune system produces antibodies against antigens on transfused foreign red blood cells, leading to their destruction.
What is haemolytic disease of the newborn?
Haemolytic disease of the newborn occurs when maternal antibodies cross the placenta and target antigens on the fetus’s red blood cells, leading to their destruction.
In which scenario does haemolytic disease of the newborn typically occur?
It typically occurs when the fetus is rhesus D positive and the mother is rhesus D negative.
How does sensitization occur in rhesus-negative mothers?
Sensitization occurs during an event like antepartum hemorrhage, exposing the mother to fetal red blood cells and prompting her to produce anti-D antibodies against the rhesus D antigen.
What can happen if a rhesus-negative mother produces anti-D antibodies?
In subsequent pregnancies, these antibodies can cross the placenta to the baby and cause haemolysis of the fetal red blood cells.
How can sensitization in rhesus-negative women be prevented?
Sensitization can be prevented by using anti-D prophylaxis.
What is paroxysmal nocturnal haemoglobinuria (PNH)?
PNH is caused by a specific genetic mutation in haematopoietic stem cells in the bone marrow, resulting in a loss of proteins that inhibit the complement cascade, leading to the destruction of red blood cells.
Is Paoxysmal nocturnal haemoglobinuria an inherited genetic condition?
No, the mutation causing PNH occurs during the patient’s lifetime, not as an inherited genetic condition.
What is the characteristic presenting symptom of Paoxysmal nocturnal haemoglobinuria?
The characteristic symptom is red urine in the morning, which contains haemoglobin and haemosiderin.
What are other presenting features of paroxysmal nocturnal haemoglobinuria?
Other features include anaemia, thrombosis (e.g., DVT, pulmonary embolism, hepatic vein thrombosis), and smooth muscle dystonia (e.g., oesophageal spasm, erectile dysfunction).
What are the main management options for PNH?
Management includes eculizumab, a monoclonal antibody targeting complement component 5 (C5), or bone marrow transplantation, which can be curative.
What is microangiopathic haemolytic anaemia (MAHA)?
MAHA involves the destruction of red blood cells as they travel through the circulation, often due to abnormal activation of the clotting system causing thrombotic microangiopathy.
How does thrombotic microangiopathy contribute to MAHA?
In thrombotic microangiopathy, blood clots partially obstruct small blood vessels, churning the red blood cells and causing their rupture (haemolysis).
What are some underlying conditions that can cause microangiopathic haemolytic anaemia?
MAHA is usually secondary to conditions such as haemolytic uraemic syndrome (HUS), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), systemic lupus erythematosus (SLE), and cancer.
What key finding is observed on the blood film of patients with MAHA?
Schistocytes (fragmented red blood cells) are a key finding on the blood film in patients with microangiopathic haemolytic anaemia.
What is prosthetic valve haemolysis?
Prosthetic valve haemolysis is a complication of prosthetic heart valves, leading to haemolytic anaemia caused by turbulence and shearing of red blood cells around the valve.
Do prosthetic valves cause haemolysis in both bioprosthetic and metallic valves?
Yes, haemolytic anaemia can occur in both bioprosthetic and metallic valve replacements, though the severity may vary between types.
What is the primary mechanism behind prosthetic valve haemolysis?
The primary mechanism is turbulence flow around the valve, which churns and breaks down red blood cells.
What are the main management strategies for prosthetic valve haemolysis?
Management includes monitoring, oral iron and folic acid supplementation, blood transfusions if severe, and possible revision surgery in severe cases.
What is sickle cell anaemia?
Sickle cell anaemia is a genetic condition that causes sickle (crescent) shaped red blood cells.
The abnormal shape makes the red blood cells more fragile and easily destroyed, leading to haemolytic anaemia. Patients with sickle cell anaemia are prone to various sickle cell crises.
Describe the pathophysiology of hemoglobin and sickle-cell disease.
–> Hemoglobin Function: Hemoglobin is the protein in red blood cells that transports oxygen. During fetal development (32-36 weeks gestation), fetal hemoglobin (HbF) decreases and adult hemoglobin (HbA) increases. At birth, hemoglobin is ~50% HbF and ~50% HbA; by six months, it consists almost entirely of HbA.
–> Sickle-Cell Disease: Caused by a mutation in the beta-globin gene on chromosome 11, it follows an autosomal recessive pattern. One abnormal gene causes sickle-cell trait (asymptomatic carrier); two abnormal genes cause sickle-cell disease.
–> Mechanism: In sickle-cell disease, the presence of hemoglobin S (HbS) causes red blood cells to become sickle-shaped under low-oxygen conditions. These rigid cells can obstruct blood flow, leading to pain, increased infection risk, and hemolytic anemia from their premature destruction.
How does sickle cell disease relate to malaria?
Sickle cell disease is more prevalent in regions traditionally affected by malaria, such as Africa, India, the Middle East, and the Caribbean.
Individuals with one copy of the sickle cell gene (sickle cell trait) experience reduced severity of malaria.
This trait provides a selective advantage, as those with sickle cell trait are more likely to survive malaria and reproduce, passing on the gene.
Consequently, the sickle cell gene is more common in malaria-endemic areas due to this evolutionary advantage.
What is the screening process for sickle cell disease?
Newborn Screening: Sickle cell disease is tested during the newborn blood spot screening test, typically conducted around five days of age.
Pregnant Women Testing: Pregnant women at high risk of being carriers of the sickle cell gene are offered testing to identify their carrier status.
What are the complications associated with sickle cell disease?
Anemia
Increased risk of infection
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
Stroke
Avascular necrosis (especially in large joints such as the hip)
Pulmonary hypertension
Gallstones
Priapism (painful and persistent penile erections)
What is sickle cell crisis?
Sickle cell crisis refers to a spectrum of acute exacerbations associated with sickle cell disease.
Crises can vary in severity, ranging from mild episodes to life-threatening complications.
They can occur spontaneously or be triggered by factors such as:
Dehydration
Infection
Stress
Cold weather
What are the common triggers for sickle cell crisis?
Dehydration: Reduced blood volume can increase sickling of red blood cells.
Infection: Infections can provoke the crisis through increased metabolic demand and inflammation.
Stress: Physical or emotional stress can lead to physiological changes that exacerbate the condition.
Cold Weather: Exposure to cold can cause vasoconstriction, reducing blood flow and triggering pain episodes.
How is sickle cell crisis managed?
–> Supportive Care: There is no specific treatment; management focuses on supportive care.
–> Hospital Admission: Maintain a low threshold for admitting patients to the hospital for monitoring and treatment.
–> Infection Management: Promptly treat any infections that may have triggered the crisis to prevent further complications.
–> Temperature Regulation: Keep the patient warm to prevent vasoconstriction and reduce pain.
–> Hydration: Ensure good hydration; intravenous (IV) fluids may be required to maintain adequate hydration levels.
–> Analgesia: Provide pain relief. Note that NSAIDs should be avoided in patients with renal impairment due to the risk of further kidney damage
What is a vaso-occlusive crisis (VOC)?
Vaso-occlusive crisis (VOC), also known as a painful crisis, is the most common type of crisis in sickle cell disease.
It occurs when sickle-shaped red blood cells clog small blood vessels (capillaries), leading to distal ischemia and subsequent pain.
What are the typical symptoms of a vaso-occlusive crisis?
Pain: Often severe, it usually presents in the hands or feet but can also affect:
Chest
Back
Other body areas
Swelling: Edema in the affected areas due to ischemia.
Fever: May accompany the pain and swelling, indicating possible infection or inflammation.
What complications can arise from a vaso-occlusive crisis?
Priapism: A painful, prolonged erection caused by blood being trapped in the penis due to vascular occlusion.
Emergency Treatment: Priapism is considered a urological emergency and may require:
Aspiration of blood from the penis to relieve pressure and restore normal blood flow.
Other interventions may be necessary if priapism persists.
What is splenic sequestration crisis?
Splenic sequestration crisis occurs when red blood cells block blood flow within the spleen.
This blockage leads to an acutely enlarged and painful spleen due to pooling of blood.
What are the symptoms and potential complications of splenic sequestration crisis?
Symptoms:
Acute splenomegaly (enlarged spleen)
Abdominal pain, particularly in the left upper quadrant
Severe anemia due to blood pooling
Signs of hypovolemic shock (e.g., low blood pressure, rapid heart rate)
Complications:
Splenic Infarction: Lack of blood flow can cause tissue death in the spleen.
Hyposplenism: Reduced function of the spleen leading to decreased immune response.
Increased Susceptibility to Infections: Particularly with encapsulated bacteria such as:
Streptococcus pneumoniae
Haemophilus influenzae
How is splenic sequestration crisis managed?
Supportive Management:
Blood transfusions to treat severe anemia.
Fluid resuscitation to address hypovolemic shock.
Preventive Measures:
Splenectomy: Surgical removal of the spleen may be considered in recurrent cases to prevent future sequestration crises.
What is aplastic crisis?
Aplastic crisis is characterized by a temporary absence of new red blood cell production.
It is commonly triggered by infection with parvovirus B19.
How does an aplastic crisis affect the body?
The infection (often parvovirus B19) leads to a decrease in erythropoiesis (red blood cell production) in the bone marrow.
This results in significant anemia (aplastic anemia) due to insufficient red blood cells to meet the body’s oxygen demands.
What symptoms are associated with aplastic crisis?
Symptoms of anemia, which may include:
Fatigue
Weakness
Pallor (pale skin)
Dizziness or lightheadedness
Shortness of breath
How is aplastic crisis managed?
Supportive Management:
Blood transfusions may be administered if anemia is severe and symptomatic.
Spontaneous Resolution:
The condition typically resolves on its own within about a week.
What is acute chest syndrome?
Acute chest syndrome occurs when the blood vessels supplying the lungs become obstructed by sickle-shaped red blood cells.
It can be triggered by vaso-occlusive crises, fat embolism, or infections.
What are the common symptoms of acute chest syndrome?
Fever
Shortness of breath
Chest pain
Cough
Hypoxia (low oxygen levels)
How is acute chest syndrome diagnosed?
A chest X-ray is performed, which typically shows pulmonary infiltrates, indicating fluid or cells in the lung tissue.
What is the management approach for acute chest syndrome?
–> Analgesia: Pain relief is crucial for comfort.
–> Good Hydration: Intravenous fluids may be needed to maintain hydration.
–> Antibiotics or Antivirals: These are administered if an infection is suspected.
–> Blood Transfusions: Given for anemia to increase red blood cell levels and oxygen-carrying capacity.
–> Incentive Spirometry: Encourages deep breathing to improve lung expansion and function.
–> Respiratory Support: Oxygen therapy, non-invasive ventilation, or mechanical ventilation may be required for severe hypoxia.
Why is acute chest syndrome considered a medical emergency?
Acute chest syndrome has a high mortality rate, making prompt recognition and treatment essential to improve patient outcomes.
What are the general management principles for sickle cell disease?
Avoid Triggers: Prevent crises by avoiding dehydration and other known triggers.
Up-to-Date Vaccinations: Ensure vaccinations are current to protect against infections.
Antibiotic Prophylaxis: Use penicillin V (phenoxymethylpenicillin) to reduce the risk of infections.
Hydroxycarbamide: Stimulates the production of fetal hemoglobin (HbF).
Crizanlizumab: A monoclonal antibody that targets P-selectin.
Blood Transfusions: Administered for severe anemia.
Bone Marrow Transplant: Considered a curative treatment option.
How does hydroxycarbamide help in sickle cell disease?
Hydroxycarbamide stimulates the production of fetal hemoglobin (HbF), which does not lead to sickling of red blood cells.
It reduces the frequency of vaso-occlusive crises, improves anemia, and may extend lifespan.
What is the role of crizanlizumab in the management of sickle cell disease?
Crizanlizumab is a monoclonal antibody that targets P-selectin, an adhesion molecule on endothelial cells and platelets.
It prevents red blood cells from sticking to blood vessel walls, thereby reducing the frequency of vaso-occlusive crises.
Why are vaccinations and antibiotic prophylaxis important in sickle cell disease?
Individuals with sickle cell disease are at increased risk for infections due to spleen dysfunction.
Vaccinations protect against common infections, and antibiotic prophylaxis with penicillin V helps to prevent serious bacterial infections.
What is disseminated intravascular coagulation (DIC), and what are its key features?
–> Definition: DIC is a serious condition characterized by the dysregulation of coagulation and fibrinolysis, leading to widespread clotting and bleeding.
–> Homeostasis Overview: Under normal conditions, coagulation and fibrinolysis are coupled. Coagulation activates the cascade resulting in thrombin production, which converts fibrinogen to fibrin, forming stable clots. The fibrinolytic system generates plasmin, which breaks down fibrin clots, producing fibrin degradation products.
Role of Plasmin: Plasmin is critical for maintaining balance, as it is essential for both coagulation and fibrinolysis.
–> Pathophysiology of DIC: In DIC, coagulation and fibrinolysis become dysregulated, leading to excessive clot formation and subsequent bleeding, regardless of the triggering event.
–> Key Mediator: Tissue Factor (TF), a transmembrane glycoprotein, is a critical initiator of DIC. It is released following vascular damage and interacts with coagulation factors, initiating the coagulation cascade.
–> Triggers of TF Release: TF is released in response to cytokines (like interleukin-1), tumor necrosis factor, and endotoxin, particularly in septic conditions.
–> Coagulation Pathways: Once activated, TF binds with coagulation factors, triggering the extrinsic pathway (via Factor VII) and subsequently the intrinsic pathway (XII to XI to IX), leading to extensive clot formation.
What are the causes of disseminated intravascular coagulation?
sepsis
trauma
obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)
malignancy
What are the diagnostic features of disseminated intravascular coagulation (DIC)?
ypical Blood Picture in DIC:
Platelets: ↓ (thrombocytopenia)
Fibrinogen: ↓
Prothrombin Time (PT): ↑ (prolonged)
Activated Partial Thromboplastin Time (APTT): ↑ (prolonged)
Fibrinogen Degradation Products: ↑
Schistocytes: Present due to microangiopathic haemolytic anaemia
How do DIC laboratory results compare with other disorders?
Warfarin Administration: PT prolonged, APTT normal, Bleeding time normal, Platelet count normal.
Aspirin Administration: PT normal, APTT normal, Bleeding time prolonged, Platelet count normal.
Heparin: PT often normal (may be prolonged), APTT prolonged, Bleeding time normal, Platelet count normal.
DIC: PT prolonged, APTT prolonged, Bleeding time prolonged, Platelet count low.
What are nosebleeds also known as, and where do they typically originate?
Nosebleeds are also known as epistaxis.
Bleeding usually originates from Kiesselbach’s plexus, located in Little’s area, which is in the anterior nasal cavity and contains a rich network of blood vessels.
What causes the bleeding in epistaxis?
The bleeding occurs when the nasal mucosa is disrupted, exposing the blood vessels in this area, making them prone to bleeding.
In which age groups are nosebleeds most common, and what can trigger them?
Nosebleeds are common in young children and older adults.
Triggers include:
Nose picking
Colds
Sinusitis
Vigorous nose-blowing
Trauma
Changes in the weather
Coagulation disorders (e.g., thrombocytopenia, Von Willebrand disease)
Anticoagulant medication (e.g., aspirin, DOACs, warfarin)
Snorting cocaine
Tumours (e.g., squamous cell carcinoma)
What symptoms may occur when a patient swallows blood during a nosebleed?
The patient may present with vomiting blood.
How is the bleeding typically characterized, and what does bilateral bleeding indicate?
Bleeding is usually unilateral.
Bilateral bleeding may indicate posterior bleeding, which presents a higher risk of aspiration of blood.
How do most nosebleeds resolve, and when might further investigation be needed?
Most nosebleeds resolve without medical assistance.
Recurrent or significant nosebleeds may require further investigation to identify underlying causes, such as thrombocytopenia or clotting disorders.
What advice can be given to patients for managing a nosebleed?
Sit up and tilt the head forwards (tilting backwards is not advised as it can direct blood toward the airway).
Squeeze the soft part of the nostrils together for 10–15 minutes.
Spit out any blood in the mouth instead of swallowing.
When should a patient with a nosebleed be admitted to the hospital, and what treatments might be provided?
Admission may be necessary if:
Bleeding does not stop after 10–15 minutes.
The nosebleed is severe.
Bleeding is from both nostrils.
The patient is haemodynamically unstable.
Treatment options include:
Nasal packing (using nasal tampons or inflatable packs).
Nasal cautery (using silver nitrate sticks).
What should be considered after treating an acute nosebleed?
Consider prescribing Naseptin nasal cream (chlorhexidine and neomycin) to reduce crusting, inflammation, and infection.
Contraindication: Do not use in patients with peanut or soya allergies.
What is thrombocytopenia and the normal range for platelet count?
Thrombocytopenia describes a low platelet count.
The normal platelet count is 150–450 x 10^9/L.
What are the causes of reduced platelet production in thrombocytopenia?
Viral infections (e.g., Epstein-Barr virus, cytomegalovirus, HIV).
B12 deficiency.
Folic acid deficiency.
Liver failure (due to reduced thrombopoietin production).
Leukaemia.
Myelodysplastic syndrome.
Chemotherapy.
Causes of Increased Platelet Destruction in Thrombocytopenia
Medications (e.g., sodium valproate, methotrexate).
Alcohol.
Immune thrombocytopenic purpura (ITP).
Thrombotic thrombocytopenic purpura (TTP).
Heparin-induced thrombocytopenia (HIT).
Haemolytic uraemic syndrome (HUS).
How does mild thrombocytopenia present?
Asymptomatic in mild cases, often found incidentally on a full blood count.
What symptoms may occur when platelet counts fall below 50 x 10^9/L in thrombocytopenia?
Easy bruising.
Prolonged bleeding times.
Nosebleeds.
Bleeding gums.
Heavy periods (menorrhagia).
Haematuria (blood in urine).
Rectal bleeding.
What are the risks and symptoms when platelet counts fall below 10 x 10^9/L in thrombocytopenia?
High risk of spontaneous bleeding, including:
Intracranial haemorrhage.
Gastrointestinal bleeding.
What are the top differential diagnoses to consider for abnormal or prolonged bleeding?
–> Thrombocytopenia (low platelet count).
–> Von Willebrand disease (deficiency of von Willebrand factor).
–> Haemophilia A (factor VIII deficiency) and –> Haemophilia B (factor IX deficiency).
–> Disseminated intravascular coagulation (usually secondary to sepsis).
What are the alternative names for Immune Thrombocytopenic Purpura (ITP)?
Autoimmune thrombocytopenic purpura
Idiopathic thrombocytopenic purpura
Primary thrombocytopenic purpura
What is the pathophysiology of Immune Thrombocytopenic Purpura (ITP)?
ITP is a condition where antibodies are created against platelets, leading to an immune response that destroys platelets, resulting in thrombocytopenia (low platelet count).
How does immune thrombocytopenic purpura normally present?
presents with purpura, which are non-blanching lesions caused by bleeding under the skin.
What general care is involved in managing Immune Thrombocytopenic Purpura (ITP)?
Care involves monitoring the platelet count, controlling blood pressure, and suppressing menstrual periods.
What is the management of immune thrombocytopenic purpura?
–> The first-line treatment for ITP is oral prednisolone
–> pooled normal human immunoglobulin (IVIG) may also be used
it raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required
–> splenectomy is now less commonly used
–> rituximab may be used to target B cells
What are the key investigations for diagnosing ITP?
–> Full blood count: Shows isolated thrombocytopenia.
–> Blood film: Assesses blood cell appearance and rules out other causes.
What is the pathophysiology of TTP?
TTP is caused by a deficiency of the ADAMTS13 protein, which normally regulates von Willebrand factor (vWF) activity. Without ADAMTS13, vWF remains active, leading to excessive platelet adhesion and the formation of tiny thrombi throughout small blood vessels. This causes:
Thrombocytopenia: Due to platelet consumption
Purpura: Resulting from low platelet counts
Tissue ischaemia: Thrombi block small vessels, leading to reduced blood supply and end-organ damage
What causes ADAMTS13 deficiency in TTP?
Inherited (Hereditary): A genetic mutation causes a deficiency in ADAMTS13 production.
Acquired (Autoimmune): Antibodies target ADAMTS13, reducing its activity.
What are the key features of TTP?
–> Rare: Typically occurs in adult females
–> Fever
–> Fluctuating neurological signs: Due to microemboli in small vessels
–> Microangiopathic haemolytic anaemia: —-> Destruction of red blood cells as they pass through the small vessel thrombi
–> Thrombocytopenia: Low platelet count due to platelet consumption in clot formation
–> Renal failure: From ischaemia caused by blocked small vessels
What are the causes of Thrombotic Thrombocytopenic Purpura (TTP)?
Post-infection: e.g., urinary tract infections, gastrointestinal infections
Pregnancy
Drugs:
Ciclosporin
Oral contraceptive pill
Penicillin
Clopidogrel
Aciclovir
Tumours
Systemic Lupus Erythematosus (SLE)
HIV
What are the treatment options for Thrombotic Thrombocytopenic Purpura (TTP)?
Treatment is guided by a haematologist and may include:
Plasma exchange
Steroids
Rituximab (a monoclonal antibody targeting B cells)
What is Heparin-Induced Thrombocytopenia (HIT) and how does it develop?
HIT involves the development of antibodies against platelets in response to heparin (typically unfractionated, but can occur with low-molecular-weight heparin).
Mechanism:
Antibodies target a protein on platelets called platelet factor 4 (PF4).
HIT antibodies bind to platelets, activating the clotting system.
This leads to a hypercoagulable state, causing thrombosis (e.g., deep vein thrombosis).
Simultaneously, the antibodies lead to platelet destruction, resulting in thrombocytopenia.
