Haematology 2 Flashcards
What are the two types of thrombosis?
Arterial - e.g. MI or stroke (high pressure system where thrombi is platelet rich so treat with anti-platelets (aspirin or clopidogrel)
Venous - e.g. DVT or PE (low pressure system where thrombi is fibrin rich - treat with anticoagulants to suppress coagulation cascade e.g. heparin or DOACs
what are some risk factors for arterial thrombosis?
- smoking
- obesity
- hypertension
- DM
- older age
- there are no inherited arterial thrombophilias
what are some risk factors for venous thrombosis?
Acquired: age, previous VTE, surgery/trauma, immobility, obesity, cancer, pregnancy, serious illness, contraceptive pill, HRT, immobility, long haul flights, polycythaemia, SLE
Inherited: thrombophilia e.g. Factor V leiden (most common), protein C or S deficiency, antithrombin deficiency, anti-phospholipid syndrome
what is a DVT?
it is a clot in the veins
can occur in any vein - but usually in major deep veins of pelvis and legs
* if they occur in other locations e.g. arm they are often idicative of a more sinister underlying cause (e.g. clotting disorder, carcinoma)
they can embolise and travel through the right side of the heart and into the lungs where it becomes lodged in the pulmonary arteries and causes a pulmonary embolism
why does a venous thromboembolism usually occur?
they usually occur secondary to stagnation of blood and hyper-coagulable states.
what is given as VTE prophylaxis to patients admitted to hospital?
if they are at increased risk of VTE they should recieve LMWH (enoxaparin). If contraindicated - warfarin or a DOAC.
Anti-embolic compression stocking are also used (unless contraindicated - in things such as significant peripheral arterial disease.
how would a DVT present?
- almost always unilateral
- calf or leg swelling
- tenderness of the calf
- superficial veins
- pitting oedema
- redness
what is Virchow’s triad?
the three main causatory factors that lead to DVT
- stasis
- hypercoaguability
- vessel wall injury
what investigations would you use for DVT?
- first of all you would perform a wells score
- D-dimer is sensitive but not specific (other conditions such as pneumonia, malignancy, heart failure, surgery, pregnancy can cause a raised d-dimer)
- USS doppler of the leg
what is included in a well score ?
active cancer (1 point) calf swelling (at least 3cm larger than other side)(1 point) prominent superficial veins (1 point) pitting oedema (1 point) swelling of entire leg (1 point) localised pain along distribution of deep vein system (1 point) paralysis or paresis or recent cast immobilisation of lower extremities (1 point) Recent bed rest >3 days or major surgery in past 12 weeks (1 point) previous history of DVT (1 point) alternative diagnosis just as likely (2 points)
DVT likely: 2 points or more
DVT unlikely: 1 point or less
what actions should you take following a Wells score?
If DVT is likely (2 points or more):
> a proximal leg vein USS should be carried out within 4 hours: if positive then the diagnosis of DVT is made and anticoagulation treatment should start. If result is negative do a d-dimer to confirm negative result
> if the USS can not be carried out within 4 hours a D-dimer test should be performed and interim therapeutic anticoagulation (a DOAC) administered whilst waiting for USS (which should be performed within 24 hours)
> if scan is negative but D-dimer is positive - stop interim anticoagulation but offer proximal leg vein USS 6 to 8 days later
if DVT is unlikely (1 point or less)
> perform a D-dimer test (should be done within 4 hours, if not, give an interim anticoagulation
>if test is -ve then DVT unlikley
> if +ve then do proximal vein USS
how is DVT managed?
The first line is apixaban or rivaroxaban (both DOACs) - offered first line following confirmation of DVT (new guidelines) - in non pregnant
If starting warfarin, must have two consecutive INR readings >2.0 before stopping LMWH (termed bridging therapy)
Continue anticoagulation for:
3 months: if there is an obvious reversible cause
Beyond 3 months if the cause is unclear, there is recurrent VTE or there is an irreversible underlying cause such as thrombophilia.
6 months - in active cancer then review.
beyond 6 months - recurrent DVT
what are the different coagulation tests?
Prothrombin time (PT) - it is prolonged by coumarins (warfarin), VK deficiency and liver disease.
Activated partial thromboplastin time (APTT) - increased in heparin treatment, haemophilia, antiphospholipid syndrome or DIC
INR - ratio of the time the time the samples takes to clot compared to the control
what clotting factors does heparin affect?
prevents activation factors 2,9,10,11
what clotting factors does warfarin affect?
affects synthesis of factors 2,7,9,10
what can cause thrombocytopenia?
reduced platelets
decreased production: congenital (malfunctioning bone barrow)
bone marrow infiltration (leukaemia, metastasis, lymphoma, myeloma, myelofibrosis),
Impaired platelet production (low B12/folate, reduced thrombopoietin (liver disease), medication e.g. methotrexate or chemo, alchohol, HIV, TB, autoimmune aplastic anaemia
Increased destruction - ITP, hypersplenism, heparin induced thrombocytopenia, DIC, thrombotic thrombocytopenia purpura.
what is myelodysplastic syndrome?
aka myelodysplasia
it is a group of clonal stem cell disorder characterised by ineffective and dysplastic haematopoiesis resulting in one or more cytopenias and a varying prediction to develop AML.
It is believed that environmental exposures, hereditary factors and gene alterations and deletions contribute to the development of a neoplastic multi-potential haematopoietic stem cell clone.
what are the diagnostic features of myelodysplasia syndrome?
It causes low levels of blood components that originate from the myeloid cell line: anaemia, neutropenia, thrombocytopenia
common in older age >70years
often asymptomatic - usually only found on lab findings
Anaemia: Fatigue, exercise intolerance, pallor, purpura, petechiae
how is myelodysplastic syndrome diagnosed?
FBC - one or more cytopenias
reticulocyte count will be inappropriately normal or low
Rule out folate and B12 and iron deficiency as cause of anaemia
Rule out HIV as a cause of any of the cytopenias
Bone marrow aspiration with iron stain - single of multilineage dysplasia (bone marrow blasts <20%)
Bone marrow biopsy - hypercellular marrow
how is myelodysplastic syndrome managed?
if asymptomatic - monitor
> haematopoietic growth factors - epoetin alpha
blood transfusion (RBC or Platelet transfusions)
if severe - chemotherapy - azacitidine
Stem cell transplant
what is ITP?
immune thrombocytopenic purpura: is an autoimmune haematological disorder characterised by isolated thrombocytopenia in the absence of an identifiable cause.
what are the two types of ITP?
Primary (acute): isolated thrombocytopenia with no identifiable cause. The thrombocytopenia is secondary to an autoimmune phenomenon and involves antibody destruction of peripheral platelets. Most commonly in children aged 2-6 years. May follow recent viral infection or immunisations. It is self limiting purpura over 1-2 weeks. There will be acute onset of muco-cutaneous bleeding)
Secondary (chronic) - includes all forms of ITP where associated medical conditions or precipitants can be identified. more common in woman, associated with other autoimmune disorders e.g. SLE, thyroid disease, autoimmune haemolytic anaemia, also seen in patients with CLL and solid tumours. Platelet autoantibodies
how does ITP present?
> common in age <10 or >65
- bleeding (signs of bleeding - bruising, petechiae, haemorrhagic bullae, bleeding gums)
- absence of systemic symptoms
how is ITP diagnosed?
FBC - thrombocytopenia
platelet autoantibodies seen in 60-70% of patients
how is ITP managed?
In children - will usually resolve spontaneously
IVIG plus prednisolone plus platelet transfusions
if this doesn’t work - mycophenolate or rituximab
what is heparin induced thrombocytopenia?
it is a severe drug reaction to heparin that can lead to life and limb threatening venous and/or arterial thromboembolism.
There is development of IgG antibodies against Heparin-platelet activation and consumption which results in thrombocytopenia. Platelt activation results in severe thrombosis (arterial or venous) and skin necrosis.
This results in thrombocytopenia and/or thrombosis
Typically it develops 5-10 days after exposure
how does heparin induced thrombocytopenia present?
necrosis at heparin injection sites
features consistent with recent venous or arterial thromboembolic event (e.g. PR,DVT, stoke, MI)
how is heparin induced thrombocytopenia managed?
stop heparin immediately and administer VK
add a non heparin alternative - e.g. fondaparinux or a direct acting oral anticoagulant
what is TTP?
Thrombotic thrombocytopenic purpura
It is a clinical syndrome characterised by microangiopathic haemolytic anaemia and thrombocytopenic purpura.
Without treatment it is typically fatal
what is the pathogenesis of TTP?
the underlying cause may involve the production of unusually large amounts of vWF multimers.
These multimers build up due to lack of ADAMTS-13 which is a protease responsible fo vWF degradation.
The lack of ADAMTS-13 is though to be secondary to an autoimmune process or a genetic mutation
The large amount of vWF with platelet membranes - this interaction triggers aggregation of circulating platelets at the sites of high intravascular stress which results in thrombi in the microvasculature system.
The blood clots in the small vessels break up RBCs leading to a haemolytic anaemia
how does TTP present?
There may be a non-specific prodrome
Severe neurological symptoms - coma, focal abnormalities, seizure
Digestive symptoms secondary to microthrombi in the bowel - nausea, vomiting, diarrhoea, abdominal pain
what investigations would you perform for TTP?
Platelet count - decreased
Hb - usually decreased
Peripheral smear - microangiopathic blood film with schistocytes
Reticulocyte count is typically raised in TTP
Urinalysis may show proteinuria
Direct Coombs test to rule out autoimmune haemolytic anaemia
how would you treat TTP?
> plasma exchange - to remove ADAMTS-13 antibody and provide ADAMTS-13 source
Corticosteroids - oral prednisolone or IV methylprednisolone
Monoclonal antibody - caplacizumab
what is DIC?
disseminated intravascular coagulation
it is an acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors
what are the causes of disseminated intravascular coagulation?
- sepsis/severe infection, major trauma or burns
- some malignancies - AML or metastatic mucin-secreting adenocarcinoma
- obstetric disorders - amniotic fluid embolisation, eclampsia, abruptio placentae, retained dead fetus syndrome
- severe organ destruction of failure - severe pancreatitis or acute hepatic failure
- vascular disorders - kasabach-merritt syndrome or giant haemangiomas, large aortic aneurysms
what are the diagnostic features of DIC?
- presence of underlying disorder
- oliguria, hypotension or tachycardia
- purpura fulminans, gangrene, acral cyanosis (systemic sigs of microvascular/macrovascular thrombosis)
- patient will be actively ill an shocked
- bleeding from mouth, nose and venepuncture sites
- widespread bruising and purpura
- vessel occlusions
- delerium and come
what investigation would you order for DIC?
FBC - platelet count decreased (severe thrombocytopenia) Prothrombin time - often prolonged APTT - unpredictable Fibrinogen - decreased D-dimer - raised
how do you manage DIC?
- treat underlying cause
- platelet transfusion and fresh frozen plasma to replace coagulation factors and coagulation inhibitors
- cryoprecipitate to replace fibrinogen and some coagulation factors
- RBC transfusions in those who bleeding profusely.
what is haemophilia?
Haemophilia is a X-linked recessive disorder of coagulation.
It is due a deficiency in coagulation factor.
Haemophilia A result from deficiency of clotting factor VIII (8).
Haemophilia B results from the deficiency of clotting factor IX (9).
*X-linked recessive inheritance - man with haemophilia -> all daughter are carriers and all sons have disease.
Mother carrier and unaffected father - half daughters carriers and half sons disease.
What are the diagnostic factors for haemophilia?
- presence of risk factors (family history, male sex, for acquired haemophilia - age >60 and autoimmune disorders.
- history of recurrent or severe bleeding
- bleeding into muscles - presents with pain and swelling of the involved area
- the hallmark of severe disease is recurrent spontaneous bleeding into joints and muscle which can lead to crippling arthritis if not treated.
- also bleeding from gums, Gi tract, urinary tract, retroperitoneal space, intracranial
- 40% of patients will present in the neonatal period with intracranial haemorrhage or prolonged oozing from the heel prick and venepuncture sites
how is haemophilia investigated?
aPTT will be prolonged
plasma factor VIII or IX are used to establish diagnosis and severity
prothrombin time will be normal
how is haemophilia managed?
Recombinant factor VIII for haemophilia A and recombinant factor IX concentrate for haemophilia B - given by IV infusion whenever there is bleeding
Prophylactic factor VIII is given to all children from the age of 2 years to reduce risk of chronic joint damage
for mild haemophilia A - desmopressin can be used (it stimulates endogenous release of factor VIII and vWF)
