1
Q
Primary hemostasis
A
Platelets and platelet function
- vessels
2
Q
Secondary
A
Coagulation
- coagulation factors
- vessel
3
Q
Tertiary
A
Fibrinolysis
- fibrinolytic molecules
- vessel
4
Q
_____ plays a role in all 3 parts of hemostasis
A
Vessel
- no test to assess vessel function/viability
- look for morphological presence via biopsy
5
Q
If endothelial cells are quiescent, they will _____ primary and secondary and _____ tertiary
A
Inhibit; enhance
- once activated, they enhance primary and secondary and inhibit tertiary
6
Q
Platelet - structure
A
Small fragments of megakaryocyte cytoplasm
- phospholipid membrane w/ glycoproteins
- open canalicular system of membrane invaginations
- cytoskeleton
7
Q
Platelet - granules
A
- tubular system of ER: stores Ca (platelet activation and TBX production)
- alpha granules: hemostasis and angiogenesis
- dense granules: Ca, Mg, ADP, ATP
- glycogen and mitochondria
8
Q
Megakaryopoiesis and thrombopoiesis
A
Thrombopoietin and other cytokines
- BM, spleen, lung (most important site of production)
- platelets released directly into the blood
9
Q
Thrombopoietin
A
- hepatocytes (dogs), renal tubular epithelium, BM stromal cells
- constitutively expressed
- plasma concentration dependent on MPL receptor numbers (present in platelets and megakaryocytes)
- inflammation: IL-6 –> TPO expression in BM
10
Q
Reticulated platelets
A
- young platelets
- increased RNA
- less than 24 hours in dogs
11
Q
Platelet concentration
A
- production
- consumption
- destruction
- shift/sequestration
- dilution
12
Q
Blood smear
A
- platelet estimation
- morphologic abnormalities
13
Q
Platelet sample
A
- EDTA
- citrate, theopylline, dipyridamole, and adenosine (CTAD tubes) may be useful for cats
- 8 hr at RT and 48 hr at 4C
- check for platelet clumping
14
Q
Platelet count
A
- impedance counters
- optical or laser flow cytometers
- CBC
- hemocytometer
15
Q
Mean platelet volume
A
Varies between analyzer, anticoagulant and storage time
- presence of cell fragments and large platelets
16
Q
Thrombocytopenia
A
Concentration is lower than the LRL
- common in Greyhounds and Shiba Inus (lower than other dogs)
- reflects a pathologic process (not a diagnosis)
17
Q
Thrombocytopenia less than 30,000/uL
A
- petechiae and ecchymosis
- mucosal bleeding (epistaxis, hematochezia, melena), hematuria, hyphema
18
Q
Pseudo-thrombocytopenia
A
- not all platelets were counted
- in vitro platelet activation or aggregation
- presence of large platelets (cats or CKCS) in impedance counters
- cold agglutinins, or anticoagulant induced, antibody-mediated agglutination
19
Q
Thrombocytopenia - shift/sequestration
A
- reversibly distributed in vascular systems (spleen)
- mild or moderate thrombocytopenia
- splenomegaly
- severe hypothermia (20 C, spleen and liver in dogs)
- endotoxemia: lung pooling in dogs (may see increased consumption)
20
Q
Thrombocytopenia - decreased production
A
- generalized BM dz or MK specific process
- idiopathic thrombocytopenia of CKCS –> maybe due to lack of production
21
Q
Thrombocytopenia - decreased production due to drugs
A
- predictable, dose-dependent –> antineoplastic chemotherapeutic agents
- idiosyncratic (sporadic)
22
Q
Thrombocytopenia - decreased production due to infection
A
Multifactorial, often include decreased production
- direct infection of MK (BVD, canine distemper)
- myelosuppressive cytokines (EIA)
- unclear (canine parvo, canine monocytic ehrlichiosis)
- FeLV (due to neoplasia)
23
Q
Thrombocytopenia - decreased production due to marrow replacement
A
Myelophthisis
- bone marrow neoplasia: primary or metastatic, physical replacement, lysis of marrow cells, competition for nutrients, secretion of inhibitors, obstruction of blood supply
- myelonecrosis: infections, neoplasia, toxicants
24
Q
Thrombocytopenia - destruction
A
Immune mediated thrombocytopenia
- platelet surface associated Ig (PSAIg)
- Ab binds directly or indirectly
- destruction by mononuclear phagocytic system
- defective immune system –> defective platelets
- absorbed antigens from neoplasm, drugs, infectious agents
25
IMT
Idiopathic or primary
- not associated to a detected disease
- could be autoimmune
- common in dogs
- Ab may target MKs
- usually < 50 x 10^3/uL, often <10
- anemia in 50%
- usually MK hyperplasia (hypoplasia is possible)
26
Drug induced IMT
Drug independent Ab
- drug not necessary for binding
- Ag of drug cross-react with platelet Ag
Drug dependent Ab
- less common in animals
- Ab binds to drug that is associated to platelet
- suspected when IMT develops a few days after drug treatment was started
27
Drug induced IMT - criteria for diagnosis
- PSAIg present
- plasma Ab bind in vitro to platelets only in presence of drug
- resolution after drug is discontinued
- relapse after drug is reintroduced
- gold salts, sulfonamides (dog)
- methimazole and propylrhiocuracil (cats)
- penicillin and TMS (horses)
28
IMT associated to infection - pathogenesis
Usually multifactorial
- cross-reactive Ab
- bacteria induced Ab production
- exposure of hidden platelet Ag
- binding of Ab to organism that is bound to platelets
- immune complex formation that adhere to platelet membrane
29
IMT associated to infection - diseases
- acute canine ehrlichiosis
- Ehrlicia and Anaplasma
- rocky mountain spotted fever
- histoplasmosis, leishmaniasis
- distemper or modified virus vaccination
- equine infectious anemia
- babesiosis
30
IMT - neonatal alloimmune thrombocytopenia
Maternal alloantibodies --> epitope on neonate's platelets
- horses, mule, foals, pigs
- must be differentiated from other causes, especially sepsis
31
IMT - neoplasia
Multifactorial
- may include immunologic mechanisms
- lymphoma (dogs and horses)
32
IMT - systemic immune mediated diseases
- SLE: evidence of increased PSAIg
| - Evan's syndrome: IMHA with IMT described in dogs (IMHA dogs prothrombotic, leading to platelet consumption)
33
Thrombocytopenia - dilution
- blood loss (acute, severe): thrombocytopenia due to consumption, mild-moderate, self-limiting
- hemodilution: crystalloids, colloids, plasma, packed erythrocytes
34
Thrombocytopenia - consumption
- platelet activation w/ accelerated consumption or use: localized IV coagulation, consumption at the site, thrombin is a potent platelet activator
- DIC
- drugs or foreign materials
- envenomation
- vasculitis or endocarditis
35
Vasculitis/endocarditis
Activated endothelial cells or exposure of subendothelium
- infections
- bacterial endocarditis
- endothelial cell damage and necrosis
- Greyhounds cutaneous and glomerular vasculopathy associated with ingestion of Shiga toxin E. coli
36
Idiopathic thrombocytopenia of CKCS
Inherited giant platelet disorder
- congenital (autosomal recessive)
- common in the breed
- macrothrombocytopenia (< 100,00/uL)
- 50 - 100,00/uL is common, but platelet crit might be normal
- no clinical bleeding problem
37
Thrombocytopenia - infectious
Decreased production
- direct infection
- immune suppression
- BM inflammation
- altered distribution
- consumption
- destruction (immune-mediated and nonimmune)
38
Thrombocytopenia - Anaplasma platys
- infect platelets
- clinical or subclinical
- mild parasitemia (may be severe)
- PCR diagnosis
39
Thrombocytopenia - neoplasms
Carcinomas, sarcomas, lymphomas, leukemias
- 10% of dogs had thrombocytopenia
- decreased production --> myelophthisis, myelodysplasia, estrogen secretion, chemotherapy
40
Thrombocytopenia - neoplasms (consumption)
- DIC
| - vasculitis or thrombosis
41
Thrombocytopenia - neoplasms (destruction)
- secondary IMT
| - hemorrhage, sepsis (due to immunosuppression), destruction (malignant histiocytic sarcoma)
42
Neoplasms - sequestration
Platelets being pooled into infected organs
- splenomegaly or hepatomegaly (hemangiosarcoma)
- organ congestion (sequestration)
43
Hypophosphatemia
Thrombocytopenia
- hyperalimentation (dogs)
- decreased platelet survival: decreased platelet ATP (decreased glycolysis)
44
Cats receiving parenteral nutrition do not have _____
Hypophosphatemia
45
Anaphylaxis
Thrombocytopenia
- mechanism incompletely characterized
- inflammatory mediators
- DIC
- immune complex interaction with platelets
46
Thrombocytosis
Platelet concentration greater than URL
- redistribution
- increased neoplasm: hemic neoplasm, reaction to other conditions
- high altitudes: RI shifted upwards
47
Hemic neoplasia - primary
Essential thrombocytosis
- chronic myeloproliferative condition
- rare in dogs and cats
- 1,000 to 5,000 x 10^3/uL
- large, pleomorphic, hypogranular
- increased numbers of MKs
48
Other chronic myeloproliferative diseases
- polycythemia vera, primary erythrocytosis, chronic myeloid leukemia
49
Acute megakaryoblastic leukemia (M7)
- subtype of myeloid leukemia
- rare dogs and cats
- > 30 of cells in BM are megakaryoblasts
- thrombocytosis or thrombocytopenia
50
Thrombocytosis - reactive
Secondary
- frequently mild to moderate
- redistribution: physiologic thrombocytosis, dogs and cats, release from spleen or lungs
51
Reactive thrombocytosis leads to ______
Increased production
- inflammation (IL-6 induced TPO production)
- nonhemic malignant neoplasia (inflammation, thrombopoietic cytokines)
52
Iron defficiency
Common, but inconsistent in dogs
- not cross reactivity with EPO
- not increased TPO or IL-6
53
Vinca alkaloids
Reactive thrombocytosis
- vincristine and vimblastine
- stimulation of thrombopoiesis
54
Recovery from thrombocytopenia
Rebound
- production exceeds destruction consumption
- withdrawal of myelosuppression
- recovery from IMT
- after blood loss
55
Thrombocytosis - increased production due to reactive
Postsplenectomy
- occasionally marked thrombocytosis
- increased TPO
- transient (weeks)
- decreased destruction
- decreased sequestration
56
Increased production due to blood loss
Chronic
- several species
- iron deficiency, inflammation, rebound, neoplasia
57
Increased production due to hypercortisolemia
Hyperadrenocorticism and exogenous
58
Function of the primary hemostatic plug
Adhesion --> perturbed endothelium or exposed subendothelium (collagen) via vWF binding to GPlb
Aggregation --> agonists (ADP, collage, PAF, thrombin), GPallbB3 via fibrinogen and vWF
59
Release
Degranulation
- fibrinogen, factor V, ADP, ATP, plasminogen
- TXA2 adn arachidonic acid
60
Facilitation of coagulation
Flipping of inner negatively charged phospholipids to outer cytoplasmic membrane
- include phosphatidilserine (PF3)
- high affinity sites for coagulation enzymes, cofactors, zymogen
61
Clot retraction
Contractile process
- activated platelets
- GPallbB3 via fibrinogen
- actin and myosin
62
BMBT
Standardized primary hemostasis test
- dogs and cats
- interobserver and intraobserver variability
- insensitive: only moderate to marked primary hemostasis defects
63
BMBT procedure
Small cut 5 mm x 1mm upper lip
- start timing when cut is made
- remove excess blood from cut with filter paper w/o disturbing the cut
- end point: when no blood is transferred to the paper filter
64
Prolonged BMBT
> 4-5 min in dogs
- thrombocytopenia
- thrombopathia (platelet dysfunction): platelets, Htc, vWF WRI --> hereditary (uncommon), acquired: secondary
- vWF: dobermans, prolonged BMBT, vWF:Ag <20%
- anemia: centrally circulating platelets
- vascular disease
- antiplatelet drugs
- afibrinogenemia
65
vWF - physiologic process
Large multimeric protein --> large molecules are more functional
- platelet adhesion
- platelet aggregation
- mostly produced by endothelial cells
- forms noncovalent complexes with factor Vlll (protective and stabilizes)
66
_____ is the most common hereditary bleeding disorder of dogs
vWF
- 1: all vWF multimers are present, in decreased concentration
- 2: deficiency of vWF with disproportionate decrease of large multimers
- 3: absence of all multimers
67
vWD - clinical and lab findings
- mild to severe mucosal bleeding
- hemarthrosis and hematomas in horses
- absence of petechiae
- prolonged BMBT
- possibly decreased PTT due to decrease of factor Vlll (in humans, not dogs)
68
Use ____ or ____ tubes for vWD
Sodium citrate or EDTA
| - vWF:Ag is stable for 8 hours at RT
69
vWD - interpretative considerations
- intraindividual variation
- exercise: increased after strenuous exercise
- pregnancy: substantial increase (dogs)
- epinephrine, endotoxin, azotemia, liver disease
70
Coagulation
Forms thrombin --> converts soluble fibrinogen into insoluble fibrin
- enzyme
- substrate: fibrinogen, proenzyme
- cofactors
- on a phospholipid surface
- presence of Ca --> mediates binding of factors onto platelet surface
71
Coagulation eynzymatic factors are mostly ____
Proteases
- primarily produced by hepatocytes
- ll, Vll, lX and X are vit K dependent
- factor lX is sex-linked (X chromosome)
72
Coagulation - nonenzymatic factors
- TF: cofactor for FVll, major activator of coagulation in vivo
- fibrinogen: positive acute-phase protein produced by hepatocytes
- FV and FVlll: markedly accelerate coagulation, facilitates surface attachment of other factors
73
___ and ____ consumed during coagulation
FV and FVlll
| - not in serum
74
Extrinsic pathway
Initiated by TF that activates factor Vlll
- initiates common pathway (factor X)
- initiates intrinsic pathway (factor IX)
- important in initiating thrombin generation
75
Intrinsic pathway
Initiated by HMWK, PK and factor Xlll contacting negatively charged surfaces (collagen)
- starts common pathway activating factor X
- inhibited by ATlll
- activated by factor Vllla --> activates factor IX
- thrombin activates factor V, Xi and Vlll (propagates and amplifies thrombin generation)
76
Common pathway
Initiated by activation of factor X
- leads to formation of thrombin from prothrombin
- thrombin forms fibrin monomers and multimers cross linked by factor Xllla
- inhibited by ATlll
77
ATlll
Produced by hepatocytes
- same size of albumin
- binds, inactivates, remove coagulation factor (lla, lXa, Xa)
- ATll:enzyme complex is cleared by hepatocytes
- markedly enhanced heparin (ex and endogenous)
78
Activated coagulation or clotting time
- sample: whole blood
- screening coagulation test evaluates surface activation (intrinsic and common)
- similar to PTT, but less sensitive
- severe thrombocytopenia can increase ACT
- standard protocol
- used to monitor heparin therapy
79
Activated partial thromboplastin time (aPTT)
Screen for intrinsic adn common
- sample: citrated blood (plasma)
- procoagulant phospholipids (partial thromboplastin), Ca
- lab RI should be used
- see changes with 70% or more decrease in activity of a factor
- decreased FXll or PK (no hemorrhage) but prolonged aPTT
80
Prothrombin time (PT)
Screening of extrinsic and common pathways
- sample: citrated blood (plasma)
- test: Ca, phospholipids, TF
- use lab RI
81
Thrombin time (TT)
Assesses transformation of fibrinogen in fibrin without the interference of thrombin generation
- sample: citrated blood (plasma)
- test: thrombin added to sample
- lab specific RI
82
Prolonged TT
Decreased fibrinogen
- hypofibrinogenemia or afibrinogenemia
- increased consumption localized coagulation or DIC
- hereditary deficiency (rare)
- dysfibrinogenemia (abnormal fibrinogen), hereditary or acquired (liver dz)
- heparinized sample (due ATlll)
- increased FDPs
- paraproteinemia (abnormal Ig due to multiple myeloma)
83
Proteins induced by vit K antagonism
Incompletely carboxylated vit K dependent factors
- due to antagonism, deficiency, absence of vit K --> normal carboxylated factors are decreased
- test: thrombotest PT, modified PT with added FV and fibrinogen added --> detects decreased activity of Fll, FVll, and X
- can be decreased due to PIVKA presence since they compete with normally carboxylated factors
84
Prolonged thrombotest PT
- vit K antagonism or deficiency
- other acquired and hereditary coagulopathies for PT excluding of FV and fibrinogen
- cats with hepatic, biliary, or inflammatory bowel disease
- heparin (endogenous or exogenous)
85
ATlll (inhibitors)
Functional test: measure ATlll function not concentration
- reported as % of either species-specific or human plasma pool
- foals have decreased activity when compared with adult horses
86
Decreased ATlll activity
- hypercoagulable (prothrombotic) states
- decreased production: liver dz, inherited dz, inflammation (decreased activity in baboons, and positive acute-phase protein in rabbits and cats), estrogens: decreased synthesis
- loss: protein-loosing nephropathy or severe hemorrhage
87
Decreased ATlll activity due to consumption
Increased hepatic clearance of complexes ATlll:F
- localized coagulation or DIC
- sepsis
- heparin therapy (LMWH): accelerates use and thus hepatic clearance of ATlll
- increased ATlll activity (unknown diagnostic utility)
88
Decreased production
- hepatic dz
- inflammation
- hyperestrogenism
89
Loss
Protein losing nephropathy
90
FIbrinolysis - process
Enzymatic degradation of fibrin
- counteracts coagulation
- initiated at the same time of coagulation
- happens on hemostatic plug
- plasmin
91
Plasmin
Degrades: fibin, fibrinogen, FVa, FVllla, vWF, HMWK
- rapidly inhibited by plasmin inhibitor
- cleared by the liver
- activated by t-PA
- fibrin and fibrinogen degradation products: used to assess fibrinolysis, cleared by liver, phagocytes and kidneys
92
Effects of increased FDPs
- prolonged PT, aPTT, TT, ACT
- impairs platelet function
- compete with fibrinogen for thrombin
- compete with fibrinogen for platelet binding sites
- associate with fibrin monomers and may disrupt polymerization
93
______ detects increased fibrinolysis due to excessive coagulation
FDPs
| - may also detect increased fibrinogenolysis
94
FDP sample
Serum
- special tubes with thrombin or botox atrax venom
- plasma: citrated plasma (24 hrs at 4 C)
95
False results
- serum samples: FDPs incorporated into the clots
- generation of FDPs during blood collection
- unspecificity of the test
96
Increased FDPs
- higher conenctration in equine neonates
- localized intravascular coagulation
- DIC
- sepsis and inflammatory conditions
- hemorrhagic fluid from body cavities
- hyperplasminemia --> increased fibrinolysis: envenomations, administration of plasminogen activators, hypotensive shock/surgical trauma/heatstroke, increased endothelial production of t-PA
97
D-dimer
Detect increased fibrinolysis due to excessive coagulation
- should not detect fibrinogen
- detects FXllla cross-linked fibrin
- sample: citrated plasma (24 hrs at 4 C)
98
Increased D-dimers
Similar for increased FDPs
- except increased fibrinogenolysis
- thromboembolic disease: specificity 80% - 94% (> 1,000 ng/mL)
99
Blood vessel biopsy
Vasculitis and thrombosis
- diseases involving small vessels
- RMSF and equine purpura hemorrhagica
- petechiae and ecchymosis
100
Vessel disorders
Gross exam, serology, imaging, biopsy
- large vessels: surgical and nonsurgical traumas, invasion, aneurysms, anomalies
- small vessels: vasculitis (infections, immune-mediated and chemical), vasculopathies (rare)
101
Blood disorders
- impaired primary hemostasis
- impaired secondary hemostasis
- excessive fibrinolysis: DIC adn some envenomations
102
Bleeding patterns
- petechiae and ecchymosis: primary hemostasis problem or small vessels
- subq hematomas and hemorrhage into blood cavities: secondary hemostasis (esp if petechiae and ecchymosis are absent)
- hemorrhages thru mucosal surface: primary or secondary hemostasis problem
103
Breed and age
- breed: helps diagnose inherited dz
| - age: young, inherited
104
Gender
Hemophilia A FVlll deficiency and hemophilia B FlX deficiency
- males are not carriers, only affected
- females can be carriers or affected (rare) --> X linked
105
Functional platelet problem: vWD or thrombopathia
- PT = WRI
- PTT = WRI
- FDPs = WRI
- TT = WRI
- platelets = WRI
- BMBT = prolonged
106
Thrombocytopenia with or without platelet functional problems
- PT = WRI
- PTT = WRI
- FDPs = WRI
- TT = WRI
- platelets = decreased
- BMBT = prolonged
107
Hepatic disease
- PT = prolonged
- PTT = prolonged
- FDPs = WRI
- TT = prolonged
- platelets = WRI
- BMBT = WRI or prolonged
108
Hepatic disease
Defects in production and clearing of procoagulants, anticoagulants, profibrinolytics and antifibrinolytics
- bleeding is uncommon
109
Hepatic disease - tests
- PT, aPTT, TT, ACT: decreased production
- FDPs and D-dimers: decreased clearance, intravascular coagulation
- thrombocytopenia due to sequestration or decreased production
- BMBT: thrombocytopenia, thrombopathia
- fibrinogen: decreased production, consumption (DIC)
- ATlll: decreased production, consumption
- thrombopathia: FDPs or unknown
110
Acquired or inherited
- PT = WRI
- PTT = prolonged
- FDPs = WRI
- TT = WRI
- platelets = WRI
- BMBT = WRI
111
Hepatic or hepatobiliary disease, vit K antagonism (increased PT before aPTT)
- PT = prolonged
- PTT = WRI
- FDPs = WRI
- TT = WRI
- platelets = WRI
- BMBT: WRI
112
Vit K antagonism (may see thrombocytopenia), hepatic disease (low normal fibrinogen)
- PT = prolonged
- PTT = prolonged
- FDPs = WRI
- TT = WRI
- platelets = WRI
- BMBT = WRI
113
Vitamin K antagonism
Bleeding is common, 3-7 days after exposure
- ingestion: hydroxycoumarins or indanediones, sweet clover or sweet grass, therapeutic coumadins, excessive coccidiostatis
- inhibit recycling of oxidized vit K
- absorbed in intestine
114
Vit K antagonism - causes
Prolonged anorexia or abnormal diet
- gut sterilization by antimicrobials
- malabsorption (intra or extrahepatic cholestasis, intestinal malabsorption disease, exocrine pancreatic insufficiency
115
Vit K tests
- PT, aPTT, ACT: decreased vit K dependent factors
| - thrombocytopenia: consumption
116
Fulminant consumptive coagulopathy (DIC)
- PT = prolonged
- PTT = prolonged
- FDPs = increased
- TT = prolonged
- platelets = decreased
- BMBT = prolonged
117
Consumptive coagulopathy
Process of accelerated or unbalanced coagulation that leads to destruction or removal of procoagulant molecules
- DIC: when this process happens throughout the vasculature (disseminated)
118
Causes of consumptive coagulopathy
- infection
- tissue injury
- malignant neoplasia
- liver failure
- heatstroke
- pancreatitis
- vascular disorders
- toxins
- immune mediated disorders
119
CC - acute fulminant
Bleeding from multiple sites
120
CC - chronic constipated
Not overly bleeding, but in fragile state
| - may decompensate --> bleeding
121
CC - diagnosis
Expect 3 or more:
- thrombocytopenia
- prolonged PT and/or PTT
- increase FDP and/or D-dimer
- decrease fibrinogen concentration
- decrease ATlll
- RBC fragments (schistocytes) on blood smear
122
Causes of abnormal hemostatic test results
- prolonged TT
- thrombocytopenia
- prolonged PTT, PT, ACT
- decreased ATlll activity
- increased FDP and D-dimers
- prolonged BMBT
- erythrocyte fragmentation
123
Dilutional coagulopathy
Dilution of blood components by colloid fluids, crystalloid fluids, plasma poor packed erythrocytes or oxyglobin solution
124
Inhibition of functional factors
Heparin administration or release from mast cells
- prolongs PTT and ACT
- PT usually has a heparin inactivator
- FDPs --> increases TT, PTT, PT, ACT, BMBT
125
Thrombosis
Formation of thrombi within vascular system
| - shift of equilibrium between prothrombotic factors and antithrombotic factors
126
Thrombosis causes
- endothelial cell activation or damage
- platelet activation
- activation of coagulation
- blood stasis
- inhibition of fibrinolysis
- deficiency or abnormalities of inhibitors
127
Thrombosis - acquired conditions
- vasculitis, endocarditis
- CHF, feline cardiomyopathy, vascular defects
- trauma
- malignant neoplasia
- sepsis, endotoxemia, equine colic and colitis
- IMHA
- hypothyroidism, hyperadrenocorticism
- ATlll deficiency
128
Thrombosis - hemostatic abnormalities
- increased D-dimers
- increased FDPs
- decreased ATlll
- thrombocytopenia
- increased TT: decreased fibrinogen
