Thrombocytopenia Flashcards
What are thrombocytes and where are they produced?
- Platelets
- Small cell fragments w/o nucleus
- Produced in BM
Avg lifespan of a platelet?
5-9 days
Where are reserve platelets stored?
Spleen
Where are old platelets destroyed?
Spleen
Normal platelet range
150-450,000
30,000 - 50,000 platelets may manifest as:
Purpura
10,000 - 30,000 platelets may cause:
Bleeding (w/minimal trauma)
Platelets less than 5,000 may cause:
Spontaneous bleeding
Define primary hemostasis
- Occurs instantly after a blood vessel endothelium injury
- Platelet plug is formed
Define secondary hemostasis
- Occurs simultaneously w/primary hemostasis
- Exposure to TF to Factor 7 and other clotting factors
- Fibrin strands to strengthen platelet plug
Define prothrombin time (PT) and what it tests
- Time to clot in presence of tissue thromboplastin
- Tests EXTRINSIC and common pathways (factors 5, 7, 10, prothrombin, fibrinogen)
Define partial thromboplastin time (PTT) and what it tests
- Time to clot in presence of kaolin (activates factor 12) and cephalin (substitute platelet phospholipid)
- Tests INTRINSIC and common pathways (factors 5, 8, 9, 10, 11, 12, prothrombin, fibrinogen)
Define bleeding time and what it tests
- Time required to stop bleeding from a standardized skin puncture
- Tests primary hemostasis (platelet number and function)
General causes of thrombocytopenia
- Decreased production (not enough platelets made in BM)
- Increased destruction (breakdown of platelets in bloodstream, spleen or liver)
- Med induced
- Other
What conditions cause decreased production of platelets?
- Aplastic anemia
- Leukemia
- Cirrhosis
- Folate/B12 deficiency
- Infections of BM
- MDS
What conditions cause increased destruction of platelets?
- ITP
- TTP
- DIC
- HIT
Define idiopathic thrombocytopenic purpura (ITP)
- Autoimmune
- Antibodies against several platelet surface antigens (present in 60% of cases)
- Results in destruction of platelets (thrombocytopenia)
Who is MC affected by ITP?
- Children (50% of cases)
- Adults are diagnosed 56-60 yo
- In adults, females MC
How do adults with ITP typically present?
With a chronic condition (idiopathic, lasts longer than 6 months)
How do children with ITP typically present?
With an acute condition (usually follows an infection, spontaneous resolution within 6 months)
Pathophys of ITP
IgG autoantibodies attack platelet membrane glycoproteins and megakaryocytes (precursor platelets)
Clinical s/s of ITP
- Petechiae, purpura, gingival bleeding
- Isolated thrombocytopenia
- NORMAL blood smear
When is BM testing indicated in ITP workup?
- Pts w/unexplained cytopenias
- Pts over 60 yo
- Pts who do not respond to therapy
What is Evans syndrome?
ITP with co-existent autoimmune hemolytic anemia
Treatment of ITP
- Only if plt count is under 20-30,000 OR significant bleeding
- Steroids, IVIG
- Platelet transfusion is CONTRAINDICATED
Describe thrombotic thrombocytopenic purpura (TTP)
- Rare disorder of blood coagulation system
- Causes extensive microscopic clots to form in small blood vessels throughout the body
Who is MC affected by TTP?
Females 3:2
AAs
Etiology of TTP
- Autoimmune (antibody that inhibits ADAMTS13 enzyme activity)
- Secondary
- Inherited (Upshaw-Schulman Syndrome)
What is Upshaw-Schulman Syndrome?
- Inherited type of TTP
- Deficiency of ADAMTS13
Pathophys of TTP
- Spontaneous aggregation of platelets, platelets are consumed (decreasing platelet count)
- Circulating platelet-vWF complexes are unopposed by ADAMTS13 resulting in microthrombi
- Microthrombi cause obstruction and shearing/fragments of RBCs (schistocytes)
What is the main defect of autoimmune TTP?
Severely decreased ADAMTS13 activity
What is the main defect of secondary TTP?
- Poorly understood
- Develop TTP in situations w/increased vWF (e.g. infection)
- ADAMTS13 activity is generally normal
Activity of ADAMTS13 in autoimmune TTP vs. secondary TTP?
- Decreased activity in autoimmune
- Normal activity in secondary
What is ADAMTS13?
- Metalloproteinase responsible for breakdown of UL-vWF
- Without proper cleavage of vWF by ADAMTS13, coagulation occurs at a higher rate (e.g. TTP)
Clinical presentation of TTP?
Pentad
- Thrombocytopenia
- Microangiopathic hemolytic anemia
- Neuro symptoms
- Renal insufficiency
- Fever
What is the pentad?
- Clinical presentation of both TTP and Hemolytic Uremic Syndrome (HUS)
- Thrombocytopenia, microangiopathic hemolytic anemia, neuro symptoms, renal failure, fever
When a patient presents with the pentad s/s, how to tell TTP vs. HUS?
- If renal failure dominates, it is usually called HUS
- MC in children
What is the MC cause of acquired renal failure in childhood?
HUS
What are TTP and HUS known as?
Systemic thrombotic microangiopathy (TMA) - leads to thrombotic events, organ damage, death
Lab findings of TTP
- Microangiopathic hemolytic anemia with thrombocytopenia
- Schistocytes on blood smear
Treatment of autoimmune TTP
Plasmapheresis and steroids
Treatment of refractory/relapsing TTP
- Immunosuppressive and steroids
- Possible splenectomy?
Treatment of hereditary TTP (Upshaw-Schluman Syndrome)
Prophylactic plasma every 2-3 wks (maintains adequate levels of functioning ADAMTS13)
Tranfusion in TTP?
Transfusion is CONTRAINDICATED (fuels coagulopathy)
Describe disseminated intravascular coagulation (DIC)
- Acquired clinical syndrome
- Widespread activation of coagulation and fibrinolysis
- Thrombi formation and bleeding
Etiology of DIC
- Severe trauma
- Sepsis
- Malignancy
- Pregnancy complications
- Liver disease
Pathophys of DIC
- Release of TF triggers over clotting within the body
- This disrupts clotting elsewhere in the body causing abnormal bleeding
Clinical presentation of DIC
- Bleeding
- Renal and hepatic dysfunction
- Respiratory dysfunction
- Shock
Lab findings of DIC
- Thrombocytopenia
- Reduced fibrinogen
- Prolonged PT/bleeding time
- Elevated D-dimer
Treatment of DIC
- Treat underlying condition
- Heparin
- FFP (temporary/may result in thrombosis)
- Platelet replacement if under 5-10,000 and hemorrhaging (temporary/may result in thrombosis)
Clinical presentation of HIT
- 5-14 days after starting Heparin
- Thrombocytopenia
- Thrombosis
Pathophys of HIT
- Antibodies against heparin are formed when it is bound to platelet factor 4 (PF4)
- Results in platelet activation and formation of clots, dropping platelet count
Treatment of HIT
- STOP heparin, replace with DTI therapy
- AVOID platelet transfusion
