BLEEDING DISORDERS Flashcards
When may normal hemostatic system go wrong?
- failed to form platelet plug
- failed to form fibrin form
Why may the platelet plug fail to form?
- vessel wall (missing components)
- platelets (Reduced # or fxn)
- VWF (hereditary d.o-AD)
What are some vascular abnormalities?
- MARFAN’S syndrome (valves affected/ lack of collagen in vessels/ hyperflexibility)
- ac
Name an acquired cause of vasculitis.
- –Henoch-schonien purpura (in kids)
- —-viral
- —-could be ITP too
- —presents as PR bleeding AND mucosal bleeding
Which vitamin deficiency results in vasculitis?
- Vitamin C deficiency
- – Scurvy
- –particularly seen in lower limbs, fundi, chest if coughing
Senile purpura
Iary hemostasis
Commonest cause of acquired thrombocytopenia.
- incr. DESTRUCTION of platelets
- more common in YOUNGER kids
WHcih 2 conditions use up platelets?
DIC
ITP
When is DIC seen
- d.t MASSIVE TISSUE damage
- —-RTA/ Wrong blood transfusion/ malignancy/ OBSTETRIC complication
What is an automimmune cause of peripheral platelet destruction?
ITP: Immune thrombocytopenic Purpura
SLE
—-isoimmune (post-transfusion and neonatal)
Causes of platelet fxn defects.
- Hereditary: surface lipoproteins missing
- Acquired (drugs - NSAIDs/ ASPIRIN/// Renal failure)
How does vWF def. present as?
Herditary or ACQUIRED
Hereditary:
- —AUTOSOMAL dominant
- common
- generally mild
Acquired causes of thrombocytopenia?
- Reduced prodn (marrow failure)
- incr. destruction
What could go wrong in IIary hemostasis?
- Multiple clotting factor defi. : could be used (DIC in sepsis
- single clottign factor deficiency (failure of prodn—hereditary= Hemophilia A (VIII)
WHat conditions result inmultiple clotting factors def.?
- LIVER FAILURE (fatty liver disease/Iary biliary cirrhosis)
- Vitamin K def. ( warfarin therapy) —–2, 7,9,10
- complex coagulopathy (DIC)
Which clotting factors REQUIRE vitamin K for prodn?
FACTORS 2, 7, 9, 10
they are carboxylated by Vit K; ESSENTIAL FOR FUNCTION
WHere is vitk sourced from?
- diet
- intestinal synthesis
Why are vit. K shots given to bbies?
—risk of hemorrhagic disease of the newborn
What is REQUIRED for Vit. K absorprtion?
- requires bile SALTS for absorption in the UPPER intestine
Causes of Vit. K deficiency.
- warfarin
- obstructive jaundice
- malabsorption
- poor dietary intake
- hemorrhagic disease of newborn
How does DIC occur?
- DUE TO MASSIVE tissue damage> Excessive and inappropriate activation of haemostatis system - exposure of TF to vascular components
- TO COUNTERACT 1., MICROVASCULAR thrombus formation occurs. (> tissue infarction> END organ failure)
- With continuous 1, and 2 > clotting factor consumption —> BRUISING, PURPURA and generalized bleeding
LIVER DISEASE and warfarin disease appears how so in bleeding screening test?
-PT and APTT both LOWERS
—PT is first to lower ——V. GOOD to monitor liver disease
(VII is first to go)
How may SEPSIS cause DIC?
- DIRECT bacterial damage and hypoxia (ENDOTOXEMIA- endotoxins trigger the RELEASE of tissue factor from the monocytes)
How may DIC be triggered in obstetric emergencies?
====placenta contains a HIGH amount of tissue factor or thromboplastic factors; so in placental abruption, DIC is greatly triggered
What malignancies cause DIC? How?
- —slowly, progressive develop. of DIC#
- —ADENOCa (Bowel and prostate cancer)
- –by release of proteolytic enzymes and expression of tissue factor
- —more thrombotic fts
How to treat DIC?
- treat underlying cause
- replacement therapy
- platelet/ plasma/ fibrinogen (cryprecipitate) replacement
How may bleeding in to the joints in hemophilia occur?
Spontaneous haemorrhages occur in tissues that are subject to MECHANICAL stress
> bleeding into joints> IRON in blood irritate the synovium
> triggers the neovascuralisation in the synovium
>easily broken vessels
Hemophilia is associated with
- LARGE and medium blood vessels
What are the 3 types of haemophilia? And how does it indicate VIII/IX levels?
- mild (<2%)
- moderate (2-5%)
- severe (>5%)–
What is prolonged in haemophilia?
- APTT
What are the clinical fts of severe haemophilia?
- recurrent haemarthroses (start at 2/3 years)
- recurrent soft tissue bleeds (bruising in toddlers)
- — prolonged bleeding after dental extraction/ surgery
How to manage Haemophilia A?
- IV Factor VIII every second day
- self administered
- —prevent massive bleeds
What occurs with reccurent joint bleeds!
- reccurent bleeding results in HAEMARTHROSES
- —-affects MOTIBILITY of joint!
What is the commonest cause of PRIMARY haemostatic failure?
thrombocytopenia!
How does vWF def. present as?
—-menorrhagia/ bleeding gums/ nose bleeds
What is the MOST COMMON hematological manifestation of AIDS?
thrombocytopenia!
Which infections causes thrombocytopenia?
MEASELS
AIDS
—–BOTH said to IMPAIR prodn of platelets!
What drugs cause thrombocytopenia?
IMPAIRS prodn: cytotoxic drugs/ thiazides/ alcohol
Immune destruct.: Quinidine/ Heparin/ Sulfa compounds
When may ineffective megakaryopoiesis occur?
What does this result in?
with MEGALOBLASTIC anaemia and paroxysmal nocturnal hemoglobinuria
—-thrombocytopenia.
In whom is haemophilia seen in?
MEN
- X-linked, hereditary d.o
Which haemophilia type is MORE common?
Haemophilia A (5x more common) -----VIII deficiency
What causes non-immunological destruction of platelets?
- thrombotic thrombocytopenic purpura
- DIC
- Giant hemangiomas
- Microangiopathic hemolytic anaemia
What is ITP?
Best rx?
- Spleen - the MAIN culprit for pathogenesis
- —-site of anti-platelet Abs and site of DESTRUCTION of IgG coated platelets
RX: if chronic ITP= Splenectomy
What does a bone marrow with incr. megakaryocyte, suggest ?
- accelerated platelet destruction
- common to all forms of thrombocytopenia
What is the risk of heparin?
WHy does it occur?
- drug- induced thrombocytopenia (sets in 1/2 weeks after administration)
- —seen more with UNfractionated heparin.
—d.t formation of IgG abs activating platelets !
How is the dx of hemophilia made?
How is it treated?
- using specific assays of Factor VIII and IX
- infusion of recombinant factor VIII and IX
Why is splenomegaly a problem?
- chronically enlarged spleen often removes single/ multiple elements of the blood
> thrombocytopenia (common), anaemia, leukocytopenia
What are the key roles of vWF?
- carrier of Factor VIII
2. binds platelets to endothelium and other platelets; def. ==> poor aggregation of platelets
WHat is seen with the lab results of vWF disease?
- raised Bleeding time
- may have slight rise in PTT (if SEVERE; factor VIII is a.w vWF)
What occurs in Heyde’s Disease?
- GI bleeding in the setting of Aortic stenosis. d.t 2 reasons:
1. Incr. in vascular malformations in the GI tract (PRONE to bleeding)
2. def. of vWF (HIGH sheering force through aortic stenosis UNCOILD vWF multimers; exposing it to ADAMTS13 enzyme) —basically an OVERACTIVITY of ADAMTS 13
