Platelet disorders Flashcards
Immune thrombocytopenia (ITP) : Definition
Immune-mediated reduction in the platelet count.
Antibodies are directed against the glycoprotein IIb/IIIa receptor on body’s platelet cells
ITP : Pathophysiology
-
Autoimmune response
* Trigger : Viral, infection or other causes
* Platelet cell receptors glycoprotein IIb/IIIa recognised as foreign
* Activates immune system
2 . Antibody formation
* IgG antibodies against platelet antigen - form antigen-antibody complexes
3 . Phagocytosis and destruction of platelets - Decreased platelet count
4 . Bone marrow compensation
* In chronic cases - Bone marrow may produce increased megakaryocytes (immature platelets)
ITP - Clinical presentation in Children
Acute presentation - following infection or vaccination
- Bruising
- Petechial or purpuric rash - non blanching
- Bleeding is less common and typically presents as epistaxis or gingival bleeding
ITP - Clinical presentation in Adults
Chronic condition : in older women
1. symptomatic patients may present with
* Petechiae, Purpura
* Bleeding (e.g. epistaxis)
* Catastrophic bleeding (e.g. intracranial) is not a common presentation
ITP : Investigation
- Full blood count: isolated thrombocytopenia
- blood film
ITP : Management
Adults
* First-line treatment : Oral prednisolone
Children
* usually, no treatment is required
* ITP resolves in around 80% of children with 6 months, with or without treatment
Haemolytic uraemic syndrome- Definition
Hemolytic Uremic Syndrome (HUS) is a disorder characterized by the presence of;
- Hemolytic anemia (destruction of red blood cells),
- Thrombocytopenia (low platelet count),
- Acute kidney injury.
It is primarily seen in children, although it can affect individuals of any age
Haemolytic uraemic syndrome-Incidence
Mostly effects children
Haemolytic uraemic syndrome : Pathophysiology
1 .Infection or Toxin Exposure:
* The initial trigger is often an infection with Shiga toxin-producing bacteria, particularly E. coli .
* The toxin can also be produced by other bacteria associated with HUS.
2 . Microangiopathy - endothelial damage to blood vessels
* Shiga toxin damages the lining of small blood vessels, leading to the formation of small blood clots (microthrombi).
3 . Platelet Activation and Aggregation
* The microthrombi cause platelets to become activated and aggregate in small blood vessels.
* Thrombocytopenia
4 . Hemolysis
* The damaged red blood cells are sheared as they pass through the microthrombi, leading to hemolysis and the release of hemoglobin.
* release of small RBC cell fragments called ‘Schistocytes’ and helmet cells
5 . Kidney Involvement:
* The microthrombi can also cause damage to the small blood vessels in the kidneys, leading to acute kidney injury.
* AKI reduces renal blood flow
* Uraemia : build up of urea 2nd to AKI
HUS : Classification
Classifications; (cause of triggering endothelial damage)
1. Atypical HUS - least common
Dysregulation of the complement system following an infection
-
Typical HUS/ D+ (Diarrhea) HUS - most common
Cause : classically Shiga toxin-producing Escherichia coli
(source : contaminated food, unpasteurised milk)
HUS : Clinical features
- Bloody diarrhoea - in D+ HUS
- Anaemia - weakness, fatigue
- Haemolytisis : jaundice
- Disseminated clots : Petechiae under the skin
HUS : Diagnosis
- Lab results : anaemia, thrombocytopenia, AKI, raised urea
- Blood film : schistocytes and helmet cells
- Stool culture : evidence of Shigella-toxin ecoli infection, PCR for shigella toxin
HUS : Management
- IV fluids - shiga like toxin clears in days to weeks,
* Abx not recommended as dead bacteria potentially release more toxins.
Plasma exchange/Dialysis if very severe manifestation
Disseminated intravascular coagulation - Pathophysiology
1 . Triggers or Underlying Conditions:
. Common triggers : include severe infections (sepsis), trauma, obstetric complications (such as placental abruption)
2 . Release of Tissue Factor:
* The triggering event damages tissues
* Tissue factor (TF), a protein that initiates the extrinsic pathway of the coagulation cascade.
3 . Activation of Coagulation Cascade:
* The coagulation cascade involves the sequential activation of various clotting factors, ultimately leading to the formation of thrombin.
4 .Thrombin Generation:
* Thrombin is a key enzyme in the coagulation cascade. It converts fibrinogen to fibrin, leading to the formation of a stable blood clot.
5 . Microvascular Thrombosis:
* formation of microvascular clots throughout the body.
* Damage RBC - schistocytes due to microangiopathic haemolytic anaemia
6 . Consumption of Clotting Factors and Platelets:
7 .Fibrinolysis Activation:
* In response to widespread clot formation, fibrinolysis (the breakdown of fibrin clots) is activated.
* increased levels of fibrin degradation products in the bloodstream.
DIC : Causes
- Sepsis
- Trauma
- Obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)
- Malignancy
