Thrombotic Disorders Flashcards
What is thrombocytopenia
describes a low platelet count
Normal platelet count
150 to 450 x 10^9/L
Causes of moderate thrombocytopenia
heparin induced thrombocytopenia (HIT), drug-induced , alcohol
liver disease, hypersplenism
viral infection
pregnancy
SLE/antiphospholipid syndrome
vitamin B12 deficiency
What drugs can induce a moderate thrombocyopenia?
quinine, diuretics, sulphonamides, aspirin, thiazides
What viral infections can induce a moderat thrombocytopenia?
EBV, HIV, hepatitis
What are causes of severe thrombocytopenia?
ITP
DIC
TTP
haematological malignancy
What is ITP?
Immune (or idiopathic) thrombocytopenic purpura (ITP) is an immune-mediated reduction in the platelet count.
Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.
How does ITP in adults compare with ITP in kids?
equal sex incidence (more common in females in adults)
Children usually have an acute thrombocytopenia that may follow infection or vaccination. In contract, adults tend to have a more chronic condition.
How does ITP in kids present ?
may follow an infection or vaccination
ITP in children has a high mortality
false
usually runs a self-limiting course over 1-2 weeks
What is the epidemiology of ITP?
more common in older females
How does ITP usually present?
may be detected incidentally following routine bloods
symptomatic patients may present with:
petichae, purpura
bleeding (e.g. epistaxis)
catastrophic bleeding (e.g. intracranial) is not a common presentation
How to manage ITP?
first-line treatment for ITP is oral prednisolone
pooled normal human immunoglobulin (IVIG) may also be used
splenectomy is now less commonly used
What is Evan’s syndrome?
ITP in association with autoimmune haemolytic anaemia (AIHA)
What does TTP stand for?
Thrombotic thrombocytopenic purpura
What is the pathophysiology of TTP?
abnormally large and sticky multimers of von Willebrand’s factor cause platelets to clump within vessels
What is the underlying enzyme deficit in TTP?
deficiency of ADAMTS13
ADAMTS13 is a metalloprotease enzyme which breaks usually down (‘cleaves’) large multimers of von Willebrand’s factor
TTP overlaps with what
overlaps with haemolytic uraemic syndrome (HUS)
Who does TTP usually present in?
rare, typically adult females
How would someone with TTP present?
fever fluctuating neuro signs due to microemboli microangiopathic haemolytic anaemia thrombocytopenia renal failure
What can trigger TTP?
post-infection e.g. urinary, gastrointestinal HIV
pregnancy
drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
tumours
SLE
What is Gestational thrombocytopenia?
relatively common condition of pregnancy that results from a combination of dilution, decreased production and increased destruction of platelets
Why would you have an increase destruction of platelets in pregnancy?
increased work of the maternal spleen leading to mild sequestration
What is the typical course of ITP?
a chronic relapsing course may be seen more frequently in women.
Differentiating between ITP and gestational thrombocytopenia often relies on what?
a careful history
Gestational thrombocytopenia may be considered more likely vs ITP if?
platelet count continues to fall as pregnancy progresses
but this is not a reliable sign
If the patient becomes dangerously thrombocytopenic in gestational thrombocytopenia then how do you treat it?
she will usually be treated with steroids and a diagnosis of ITP assumed
What would you do with a woman who is found to have low platelets during a booking visit or those with a previous diagnosis of ITP?
tested for serum antiplatelet antibodies for confirmation.
Why is it important to differentiate between ITP and gestational thrombocytopenia
Gestational thrombocytopenia doesn’t affect the neonate
BUT ITP can do if maternal antibodies cross the placenta
How do you approach the thrombocytopenic neonate?
Depending on the degree of thrombocytopenia in the newborn, platelet transfusions may be indicated.
Serial platelet counts can also be performed to see whether there is an inherited thrombocytopenia.
Drug-induced thrombocytopenia is probably immune-mediated
tru
What can meds cause Drug-induced thrombocytopenia
quinine
abciximab
NSAIDs
diuretics: furosemide
antibiotics: penicillins, sulphonamides, rifampicin
anticonvulsants: carbamazepine, valproate
heparin
When should you offer platelet transfusions?
patients with a platelet count of <30 x 10 ^9 with clinically significant bleeding
threshold is higher in severe bleeding
Which WHO bleeding grade patients should be offered platelet transfusions?
World Health organisation bleeding grade 2- e.g. haematemesis, melaena, prolonged epistaxis
In severe bleeding, what is the MAXIMUM platelet count in which transfusion can be offered?
And what WHO bleeding grade would this be?
Platelet thresholds for transfusion are higher (maximum < 100 x 10 ^9) for patients with severe bleeding
World Health organisation bleeding grades 3&4 OR
bleeding at critical sites, such as the CNS
Patients with bleeding at critical sites, such as the CNS should be offered platelet transfusion if their count is<30 x 10 9
FALSE
bleeding at critical sites, such as the CNS = severe bleeding
therefore
Platelet thresholds for transfusion are higher (maximum < 100 x 10^ 9) for patients with severe bleeding
Which transfusion type has the highest risk of bacterial contamination?
Platelet transfusion.
For Platelet transfusion for thrombocytopenia before surgery/ an invasive procedure. Aim for plt levels of?
> 50×10^9/L for most patients
50-75×10^9/L if high risk of bleeding
100×10^9/L if surgery at critical site
If no active bleeding or planned invasive procedure what is the platelet threshold for plt transfusion?
A threshold of 10 x 109 except where platelet transfusion is contradindicated or there are alternative treatments for their condition
Which conditions would you usually not perform transfusion for and why
Chronic bone marrow failure
Autoimmune thrombocytopenia
Heparin-induced thrombocytopenia, or
Thrombotic thrombocytopenic purpura
platelet transfusion is contradindicated or there are alternative treatments for their condition
Under homeostatic conditions, coagulation and fibrinolysis are coupled
true
The activation of the coagulation cascade yields what that converts what to what
thrombin
fibrinogen
fibrin
What is the final product of hemostasis?
stable fibrin clot
What does The fibrinolytic system do?
breaks down fibrinogen and fibrin.
Activation of the fibrinolytic system generates plasmin (in the presence of thrombin) which is responsible for the lysis of fibrin clots.
The breakdown of fibrinogen and fibrin results in polypeptides (fibrin degradation products)
What is a key factor to the function of the fibrinolytic system
plasmin in the presence of thrombin
plasmin is critical, as it is the central proteolytic enzyme of coagulation and is also necessary for fibrinolysis.
What is the pathophysiology of Disseminated intravascular coagulation?
In DIC, the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding.
Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions.
true
One critical mediator of DIC is the release of what?
transmembrane glycoprotein (tissue factor =TF).
Why does DIC readily develops in patients with extensive trauma?
TF present on the surface of many cell types (including endothelial cells, macrophages, and monocytes)
TF is also abundant in tissues of the lungs, brain, and placenta
Sets off coagulation cascade
TF is released in response to exposure to?
cytokines (particularly interleukin 1), tumour necrosis factor, and endotoxin.
This plays a major role in the development of DIC in septic conditions
TF is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage
true
Which factors are associated with extrinsic pathway?
Factor VII
Which factors are associated with intrinsic pathway?
I, II, IX, X, XI, and XII
Describe how TF sets off the coagulation cascade?
Upon activation, TF binds with coagulation factors
that then triggers the extrinsic pathway (via Factor VII)
which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation.
What are some causes of DIC?
sepsis
trauma
obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)
malignancy
What is the typical blood pictureof DIC?
low platelets
prolonged APTT, prothrombin and bleeding time
fibrin degradation products are often raised
What might you see in the blood films for DIC?
schistocytes due to microangiopathic haemolytic anaemia
What is Factor V Leiden?
activated protein C resistance
What is the most common INHERITED thrombophilia
Factor V Leiden
Pathophysiology of FVL?
It is due to a gain of function mutation in the Factor V Leiden protein. The result of the mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal. This explains the alternative name for factor V Leiden of activated protein C resistance,
Describe pathophysiology of FVL in terms of heterozygotes and homozygotes
Heterozygotes have a 4-5 fold risk of venous thrombosis. Homozygotes have a 10 fold risk of venous thrombosis but the prevalence is much lower at 0.05%.
Screening for factor V Leiden is recommended
false
ot recommended, even after a venous thromboembolism. The logic behind this is that a previous thromboembolism itself is a risk factor for further events and this should dictate specific management in the future, rather than the particular thrombophilia identified.
