DSA: Platelet Disorders Flashcards
thrombocytopenia happens in what two conditions?
- decreased production of platelets
- increased destruction/sequestration of platelets
Thrombocytosis occurs in what two general conditions?
- overproduction of platelets (ET)
- Increased platelet release form marrow/storage areas in response to an inflammatory stimulus (reactive thrombocytosis)
What are the causes that will give us thrombocytopenia due to decreased platelet production?
- TCP due to bone marrow failure
- bone marrow infiltration
- chemotherapy and irradiation
- nutritional deficiencies (folate or B12)
- cyclic thrombocytopenia
EOD for thrombocytopenia due to bone marrow failure
- may be congenital or acquired
- most congenital marrow failure disorders present in childhood
clinical findings for bone marrow failure
- aplastic anemia
- in MDS, there is cytopenias but the marrow cellularity is not decreased
What is more suggestive of MDS?
-macrocytosis, ringed sideroblasts, dysplasia of hematopoietic elements, or cytogenetic abnormalities
What are the causes of thrombocytopenia because of increased platelet destruction?
- Immune thombocytopenia
- Thrombotic Microangiopathy
- Heparin-induced thrombocytopenia
- DIC
EOD for immune thrombocytopenia
- isolated thrombocytopenia
- assess for any new causative meds and HIV and hep C infections
- ITP is a diagnosis of exclusion
Clinical findings for ITP
- mucocutaneous bleeding
- bruising
- nosebleeds
- isolated thrombocytopenia
- infection is excluded
Tx for ITP
-if <20,000, treat them, if not, just observe
-short course of corticosteroids and maybe IVIG
-
EOD for thrombotic microangiopathy (TMA)
- Microangiopathic hemolytic anemia and thrombocytopenia, in the absence of another plausible explanation
- fever, neuro abnormalities, and kidney disease may happen too, but not required for diagnosis
- kidney dysfunction is more common and more severe in HUS
What diseases do TMA’s include?
TTP and HUS fuh sho
What antibodies will TTP have?
ADAMTS13
-it normally cleaves vWF
What is HUS usually related to?
the shiga-toxin from E. Coli O157:H7
-they usually have diarrhea or something like that
clinical findings in TMA
the typical pentad for TTP
-microangiopathic hemolytic anemia, thrombocytopenia, fever, kidney disease, and neuro system abnormalities
Tx of TMA
immediate administration of plasma exchange!!!
EOD for Heparin-Induced Thrombocytopenia
- thrombocytopenia within 5-14 days of exposure to heparin
- decline in baseline platelet count of 50% or greater
- thrombosis occurs in up to 50% of cases; bleeding is uncommon
What does HIT result from
IgG antibodies to heaprin-platelet factor 4 (PF4) and PF2 complexes
-leads to prothrombotic state…. takes up all the platelets
Tx for HIT
- immediately discontinue all forms of heparin
- do ultrasound to rule out DVT
- DTI.. direct thrombin inhibitor
What is used for prophylaxis or tx of HIT?
Argatroban
What is used for percutaneous coronary intervention
Bivalirudin
EOD for Disseminated intravascular coagulation
- frequent cause of thrombocytopenia in hospitalized patients
- pronlonged activated partial thromboplastin time and prothrombin time
- thrombocytopenia and decreased fibrinogen levels
Clinical findings of DIC?
- bleeding at multiple sites
- trousseau syndrome for malignancy related DIC
- prolonged PT and PTT
- elevation in D-dimer
- schistocytes
Tx of DIC
- treat the underlying disorder that’s causing it
- evacuation of uterus for HELLP
- trousseau: treat underlying malignancy
- immediate intiation of chemo for APL (acute promyelocytic leukemia) associate DIC
What is HELLP syndrome
form of DIC that sucks a lot of ass
- hemolysis, elevated liver enzymes, low platelets,
- peri partum women
Drug induced thrombocytopenia
-7 to 14 days after exposure
-just stop…
chemotherapeutic agents do this a lot
Posttransfusion purpura
- rare
- sudden onset TCP in someone who recently had transfused Red cells
- multiparous women
von Willebrand disease type 2B
- leads to chronic, mild TCP via abnormal vWF molecule that binds platelets with increased affinity
- aggregation and clearance
Platelet sequestration
- 1/3 of platelets are sequestered in the spleen
- so, it is probably big in TCP
Pregnancy
-expansion of blood volume
Infection or sepsis
-just treat with antimicrobials
Pseudothrombocytopenia
- results from EDTA anticoagulant-induced platelet clumping
- this phenomenon usually disappears when blood is collected in a tube containing citrate anticoagulant
Bernard-Soulier syndrome (BSS)
- auto recessive
- reduced or abnormal platelet membrane expression of glycoprotein Ib/IX
Glanzmann thrombasthenia
- IIb/IIIa receptors are messed up
- they bind fibrinogen to vWF
- auto recessive
Storage pool disease
defects in release of alpha or dense (delta) platelet granules, or both
lab values for BSS
- large platelets
- prolonged bleeding time
- addition of normal platelets does the trick
labs for Glanzmann
-marked impairment of aggregation in response to stimulation with typical agonists
Albinism associated storage pool disease
defective dense granules in disorders of oculocutaneous albinism such as Hermansky-Pudlak and Chediak-Higashi syndromes
non albinism associated storage pool disease
-defective dense granules in Ehlers-Danhlos and Wiskott-Aldrich syndromes
Quebec platelet disorder
- mild TCP
- abnormal platelet factor V molecule
- prolonged bleeding time
- platelet transfusion doesn’t work here
Tx of Qualitative platelet disorders
- transfusion of normal platelets
- can use DDAVP, antifibrinolytic agents, and recombinant huan activated factor VII too
EOD for congenital disorders of platelet function
- usually diagnosed in childhood
- family history is usually positive
- may be diagnosed in adulthood when there is excessive bleeding
Hemophilia A EOD
congenital deficiency of coagulation factor VIII
Hemophilia B EOD
congenital deficiency of coagulation factor IX
Hemophilia EOD
- recurrent hemarthroses and arthropathy
- risk of development of inhibitory antibodies to factor VIII or factor IX
- in many older patients, infection with HIV or hepatitis C virus from receipt of contaminated blood products
Is Hemophilia X-linked or autosomal
X-linked recessive!!!
-so, lots of male patients
how do we separate severe, mild, and moderate hemophilia?
- <1%
- > 5%
- between 1-5%
tx of hemophilia
plasma-derived or recombinant factor VIII or IX products
-DDAVP for mild kinds
What is DDAVP again?
desmopressin acetate
-can be used for mild hemophilia
vWD EOD
- the most common inherited bleeding disorder
- vWF binds platelets to subendothelial surfaces, aggregates platelets, and prolongs the half-life of factor VIII
most common type of vWD?
type 1
-quantitative abnormality
symptoms of vWD
mild to moderate platelet-type bleeding
- type 3 is severe
- type 2 is aight and arises in childhood
tx of Vwd
type 1: DDAVP
type 2: DDAVP, vWF product
Type 3: vWF product!!!
factor XI deficiency
- hemophilia C
- auto recessive
- Jews
- FFP is the treatment if XI isn’t available
- adjunctive aminocaproic acid
Which type of vWD is the only one that has RIPA (ristocetin-induced platelet aggregation)?
Type 2b
-large multimers dereased or absent
What is DIC caused by?
excessive tissue factor exposure or release
- results in decreases in the activity of clotting factors
- Pt and PTT are pronlonged
What is Fondaparinux and how does it work
- it’s an anticoagulant
- no effective neutralizing agent
- works to indirectly inhibit factor Xa through binding to antithrombin
- metabolized by the kidneys so watch out
What does Heparin do?
- parenteral anticoagulant
- binds to antithrombin 3 and inhibits Xa
- makes thrombin and antithrombin meet up
- LMWH is cleared by renal and is more predictable
What does warfarin do?
- Vit K antagonist
- inhibits the activity of the Vit K dependent carboxylase that is important for the posttranslational modification of coagulation factors II, VII, IX , and X
What is Dabigatran?
-a direct acting oral anticoagulant (DOAC)
What is Rivaroxaban?
-oral direct factor Xa inhibitor
When is unfrationated heparin indicated?
if concomitant thrombolysis is being considered
how long should DVT/PE patients be on anticoag therapy?
3 months minimum
What guides the dosing of Warfarin?
the international normalized ratio
-INR
What do we have to do to a PE/DVT patient first before we give them a DOAC (oral anticoag)?
- they must first recieve 5-10 days of parenteral anticoagulation
- then transitioned to the oral agent
What do we add on to people who have a very high risk PE: PE with persistent hemodynamic instability?
add thrombolytic therapy along with the anticoagulant
-**should only be considered in patients who have a low risk of bleeding
EOD for Essential thrombocytosis
- elevated platelet count in absence of other causes
- normal red blood cell mass
- absence of bcr/abl gene (Ph chromsome)
Symptoms of ET
- 50 to 60 y/o
- elevated platelet count
- risk of thrombosis rises with age
- eythromelalgia
- mucosal bleeding is less common
- paresthesias
What is ET symptoms like erythromelalgia reliably relieved by?
aspirin
what does the bone marrow look like on ET?
lots of megakaryocytes
what do we need to differentiate ET from
- =CML
- THat’s why we have to test for the philadelphia chromosome
Tx of ET
- control the platelet count
- treatment of choice is HYDROXYUREA
ET prognosis
good
-major source of morbidity is thrombosis
